A Novel Strategy for Physiologically Based Predictions of Human Pharmacokinetics

Jones, Hannah M; Parrott, Neil; Jorga, Karin; Lav??, Thierry

doi:10.2165/00003088-200645050-00006

Cited by 353Pharmaceutical studies and practicesPharmacogenetics and Drug MetabolismAnimal testing and alternatives

A Novel Strategy for Physiologically Based Predictions of Human Pharmacokinetics

Jones, Hannah M, Parrott, Neil, Jorga, Karin, Lav??, Thierry·2006·Clinical Pharmacokinetics

DOI 10.2165/00003088-200645050-00006

Open this paper in CoChat — free account

Abstract

Background The major aim of this study was to develop a strategy for predicting human pharmacokinetics using physiologically based pharmacokinetic (PBPK) modelling. This was compared with allometry (of plasma concentration-time profiles using the Dedrick approach), in order to determine the best approaches and strategies for the prediction of human pharmacokinetics.Methods PBPK and Dedrick predictions were made for 19 F. Hoffmann-La Roche compounds. A strategy for the prediction of human pharmacokinetics using PBPK modelling was proposed in this study. Predicted values (pharmacokinetic parameters, plasma concentrations) were compared with observed values obtained after intravenous and oral administration in order to assess the accuracy of the prediction methods.Results By following the proposed strategy for PBPK, a prediction would have been made prospectively for approximately 70% of the compounds. The prediction accuracy for these compounds in terms of the percentage of compounds with an average-fold error of <2-fold was 83%, 50%, 75%, 67%, 92% and 100% for apparent oral clearance (CL/F), apparent volume of distribution during terminal phase after oral administration (V(z)/F), terminal elimination half-life (t(1/2)), peak plasma concentration (C(max)), area under the plasma concentration-time curve (AUC) and time to reach C(max) (t(max)), respectively. For the other 30% compounds, unacceptable prediction accuracy was obtained in animals; therefore, a prospective prediction of human pharmacokinetics would not have been made using PBPK. For these compounds, prediction accuracy was also poor using the Dedrick approach. In the majority of cases, PBPK gave more accurate predictions of pharmacokinetic parameters and plasma concentration-time profiles than the Dedrick approach.Conclusions Based on the dataset evaluated in this study, PBPK gave reasonable predictions of human pharmacokinetics using preclinical data and is the recommended approach in the majority of cases. In addition, PBPK modelling is a useful tool to gain insights into the properties of a compound. Thus, PBPK can guide experimental efforts to obtain the relevant information necessary to understand the compound's properties before entry into human, ultimately resulting in a higher level of prediction accuracy.

Integrity signals

Registry

Crossref · 10.2165/00003088-200645050-00006

Cites

76 of 76 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

PBPK modelling has been shown to be superior to empirical scaling.
“Physiologically based pharmacokinetic modelling has been shown to be superior to empirical scaling [16, 18], but the benefits of the PBPK approach go beyond the accuracy of the prediction to include an improved mechanistic understanding.”
From Physiologically Based Pharmacokinetic Modelling for First-In-Human Predictions: An Updated Model Building Strategy Illustrated with Challenging Industry Case Studies (2019) · cites this paper as [16]
PBPK modelling, with verification of predictive performance first performed in preclinical species, is superior to empirical methods for predicting pharmacokinetics.
“A seminal paper from Jones et al. [16] first demonstrated that PBPK modelling, with verification of predictive performance first performed in preclinical species, is superior to empirical methods for predicting pharmacokinetics.”
From Physiologically Based Pharmacokinetic Modelling for First-In-Human Predictions: An Updated Model Building Strategy Illustrated with Challenging Industry Case Studies (2019) · cites this paper as Jones et al. [16]
It is not surprising that the PhRMA application of PBPK modelling resulted in poor predictions, particularly in comparison to other assessments that used industry best practice.
“Given the importance of assessing the ability to predict a compound's pharmacokinetic properties in preclinical species and for appropriate mechanistic studies to inform model development as appropriate, it is not surprising that the Pharmaceutical Research and Manufacturers of America application of PBPK modelling resulted in poor predictions, particularly in comparison to other assessments that”
From Physiologically Based Pharmacokinetic Modelling for First-In-Human Predictions: An Updated Model Building Strategy Illustrated with Challenging Industry Case Studies (2019) · cites this paper as [16]

Physiological Parameter Values for Physiologically Based Pharmacokinetic Models
Brown, R. P., Delp, M. D., Lindstedt, S. L., Rhomberg, L. R., & Beliles, R. P. (1997) · Toxicology and Industrial Health · doi:10.1177/074823379701300401 · Cited by 1,408 · see citing works
Physicochemical High Throughput Screening: Parallel Artificial Membrane Permeation Assay in the Description of Passive Absorption Processes
Kansy, M., Senner, F., & Gubernator, K. (1998) · Journal of Medicinal Chemistry · doi:10.1021/jm970530e · Cited by 1,304 · see citing works
Prediction of Human Clearance of Twenty-Nine Drugs from Hepatic Microsomal Intrinsic Clearance Data: An Examination of In Vitro Half-Life Approach and Nonspecific Binding to Microsomes
Obach, R. S. (1999) · Drug Metabolism and Disposition · doi:10.1016/s0090-9556(24)14938-0 · Cited by 1,232 · see citing works
The Prediction of Human Pharmacokinetic Parameters from Preclinical and in Vitro Metabolism Data
Obach, R. S., Baxter, J. G., Liston, T. E., Silber, B. M., Jones, B. C., Macintyre, F., Rance, D. J., & Wastall, P. (1997) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)36999-x · Cited by 987 · see citing works
Utility of in vitro drug metabolism data in predicting in vivo metabolic clearance
Brian Houston, J. (1994) · Biochemical Pharmacology · doi:10.1016/0006-2952(94)90520-7 · Cited by 925 · see citing works
Characterization of Interintestinal and Intraintestinal Variations in Human CYP3A-Dependent Metabolism
Paine, M. F., Khalighi, M., Fisher, J. M., Shen, D. D., Kunze, K. L., Marsh, C. L., Perkins, J. D., & Thummel, K. E. (1997) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)37149-6 · Cited by 790 · see citing works
Physiologically Based Pharmacokinetic Modeling 1: Predicting the Tissue Distribution of Moderate-to-Strong Bases
Rodgers, T., Leahy, D., & Rowland, M. (2005) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.20322 · Cited by 776 · see citing works
The prediction of human pharmacokinetic parameters from preclinical and in vitro metabolism data
Sun, K. (2005) · Chinese New Drugs Journal · Cited by 764 · see citing works
Predicting the Impact of Physiological and Biochemical Processes on Oral Drug Bioavailability
Agoram, B., Woltosz, W. S., & Bolger, M. B. (2001) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(01)00179-x · Cited by 651 · see citing works
Interspecies scaling, allometry, physiological time, and the ground plan of pharmacokinetics
Boxenbaum, H. (1982) · Journal of Pharmacokinetics and Biopharmaceutics · doi:10.1007/bf01062336 · Cited by 648 · cited 4× · see citing works
“[5,25,45] In contrast, allometric scaling has long been the dominant method for interspecies’ scaling;[2,3,6,7] however, owing to its empirical nature and its failure to account for differences in pharmacokinetics across 0.”
BackgroundMethodInfluential
Advances in Drug Research
Bernard, Testa, M., Meyer, U., & Testa, B. (1964) · Academic Press eBooks · Cited by 609 · see citing works
Prediction of Pharmacokinetics Prior to In Vivo Studies. 1. Mechanism‐Based Prediction of Volume of Distribution
Poulin, P., & Theil, F. (2002) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.10005 · Cited by 568 · see citing works
A Comparison of Physiochemical Property Profiles of Development and Marketed Oral Drugs
Wenlock, M. C., Austin, R. P., Barton, P., Davis, A. M., & Leeson, P. D. (2003) · Journal of Medicinal Chemistry · doi:10.1021/jm021053p · Cited by 552 · see citing works
Prediction of in vivo drug metabolism in the human liver from in vitro metabolism data
Iwatsubo, T., Hirota, N., Ooie, T., Suzuki, H., Shimada, N., Chiba, K., Ishizaki, T., Green, C. E., Tyson, C. A., & Sugiyama, Y. (1997) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(96)00184-2 · Cited by 479 · see citing works
A compartmental absorption and transit model for estimating oral drug absorption
Yu, L. X., & Amidon, G. L. (1999) · International Journal of Pharmaceutics · doi:10.1016/s0378-5173(99)00147-7 · Cited by 455 · see citing works
The Influence of Nonspecific Microsomal Binding on Apparent Intrinsic Clearance, and Its Prediction from Physicochemical Properties
Austin, R. P., Barton, P., Cockroft, S. L., Wenlock, M. C., & Riley, R. J. (2002) · Drug Metabolism and Disposition · doi:10.1124/dmd.30.12.1497 · Cited by 413 · see citing works
Animal Scale-Up
Dedrick, R. L. (1973) · Journal of Pharmacokinetics and Biopharmaceutics · doi:10.1007/bf01059667 · Cited by 397 · see citing works
Man versus Beast: Pharmacokinetic Scaling in Mammals
Mordenti, J. J. (1986) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.2600751104 · Cited by 391 · see citing works
Untitled work
(2001) · PubMed · Cited by 316 · see citing works
Estimation of the increase in solubility of drugs as a function of bile salt concentration
Mithani, S. D., Bakatselou, V., TenHoor, C. N., & Dressman, J. B. (1996) · Pharmaceutical Research · doi:10.1023/a:1016062224568 · Cited by 303 · see citing works
Prediction of Pharmacokinetics Prior to In Vivo Studies. II. Generic Physiologically Based Pharmacokinetic Models of Drug Disposition
Poulin, P., & Theil, F. (2002) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.10128 · Cited by 303 · see citing works
Prediction of Hepatic Clearance from Microsomes, Hepatocytes, and Liver Slices
Houston, J. B., & Carlile, D. J. (1997) · Drug Metabolism Reviews · doi:10.3109/03602539709002237 · Cited by 302 · see citing works
Whole Body Pharmacokinetic Models
Nestorov, I. A. (2003) · Clinical Pharmacokinetics · doi:10.2165/00003088-200342100-00002 · Cited by 290 · see citing works
Transporters involved in the elimination of drugs in the kidney: organic anion transporters and organic cation transporters.
Dresser, M., Leabman, M. K., & Giacomini, K. (2001) · Journal of Pharmacy and Science · doi:10.1002/1520-6017(200104)90:4 · Cited by 285 · see citing works
Nonspecific binding to microsomes: impact on scale-up of in vitro intrinsic clearance to hepatic clearance as assessed through examination of warfarin, imipramine, and propranolol.
Obach, R. S. (1997) · PubMed · Cited by 281 · see citing works
Interspecies Pharmacokinetic Scaling and the Evolutionary-Comparative Paradigm
Boxenbaum, H. G. (1984) · Drug Metabolism Reviews · doi:10.3109/03602538409033558 · Cited by 270 · see citing works
Correlation of Biliary Excretion in Sandwich-Cultured Rat Hepatocytes and In Vivo in Rats
Liu, X., Chism, J. P., LeCluyse, E. L., Brouwer, K. R., & Brouwer, K. L. R. (1999) · Drug Metabolism and Disposition · doi:10.1016/s0090-9556(24)15299-3 · Cited by 228 · see citing works
Comparison of the Use of Liver Models for Predicting Drug Clearance Using in Vitro Kinetic Data from Hepatic Microsomes and Isolated Hepatocytes
Ito, K., & Houston, J. B. (2004) · Pharmaceutical Research · doi:10.1023/b:pham.0000026429.12114.7d · Cited by 224 · see citing works
A COMPREHENSIVE QUANTITATIVE AND QUALITATIVE EVALUATION OF EXTRAPOLATION OF INTRAVENOUS PHARMACOKINETIC PARAMETERS FROM RAT, DOG, AND MONKEY TO HUMANS. I. CLEARANCE
Ward, K. W., & Smith, B. R. (2004) · Drug Metabolism and Disposition · doi:10.1124/dmd.32.6.603 · Cited by 212 · see citing works
Thiopental Pharmacokinetics
Bischoff, K. B., & Dedrick, R. L. (1968) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.2600570814 · Cited by 211 · see citing works
Biorelevant Dissolution Testing to Predict the Plasma Profile of Lipophilic Drugs After Oral Administration
Nicolaides, E., Symillides, M., Dressman, J., & Reppas, C. I. (2001) · Pharmaceutical Research · doi:10.1023/a:1011071401306 · Cited by 208 · see citing works
Utility of physiologically based pharmacokinetic models to drug development and rational drug discovery candidate selection
Theil, F., Guentert, T. W., Haddad, S., & Poulin, P. (2003) · Toxicology Letters · doi:10.1016/s0378-4274(02)00374-0 · Cited by 201 · see citing works
SUBSTRATE DEPLETION APPROACH FOR DETERMINING IN VITRO METABOLIC CLEARANCE: TIME DEPENDENCIES IN HEPATOCYTE AND MICROSOMAL INCUBATIONS
Jones, H. M., & Houston, J. B. (2004) · Drug Metabolism and Disposition · doi:10.1124/dmd.104.000125 · Cited by 190 · see citing works
Self-citation
Interspecies correlation of plasma concentration history of methotrexate (NSC-740).
Dedrick, R. L., Bischoff, K. B., & Zaharko, D. S. (1970) · PubMed · Cited by 184 · see citing works
Untitled work
(1998) · PubMed · Cited by 176 · see citing works
Inter‐individual variability in levels of human microsomal protein and hepatocellularity per gram of liver
Wilson, Z., Rostami‐Hodjegan, A., Burn, J. L., Tooley, A., Boyle, J., Ellis, S. W., & Tucker, G. T. (2003) · British Journal of Clinical Pharmacology · doi:10.1046/j.1365-2125.2003.01881.x · Cited by 175 · see citing works
Measurement of interstitial albumin in human skeletal muscle and adipose tissue by open-flow microperfusion
Ellmerer, M., Schaupp, L. A., Brunner, G. A., Sendlhofer, G., Wutte, A., Wach, P., & Pieber, T. R. (2000) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2000.278.2.e352 · Cited by 170 · see citing works
Forecasting the In Vivo Performance of Four Low Solubility Drugs from Their In Vitro Dissolution Data
Nicolaides, E., Galia, E., Efthymiopoulos, C., Dressman, J., & Reppas, C. I. (1999) · Pharmaceutical Research · doi:10.1023/a:1018959511323 · Cited by 165 · see citing works
Prediction of hepatic metabolic clearance based on interspecies allometric scaling techniques and in vitro-in vivo correlations
Lav??, T., Coassolo, P., & Reigner, B. (1999) · Clinical Pharmacokinetics · doi:10.2165/00003088-199936030-00003 · Cited by 162 · see citing works
Self-citation
The importance of nonspecific binding in in vitro matrices, its impact on enzyme kinetic studies of drug metabolism reactions, and implications for in vitro-in vivo correlations.
Obach, R. S. (1996) · Drug Metabolism and Disposition · doi:10.1016/s0090-9556(25)08404-1 · Cited by 134 · see citing works
Concepts in Biochemical Pharmacology
Gillette, J. R., & Mitchell, J. R. (1975) · Springer eBooks · doi:10.1007/978-3-642-46314-3 · Cited by 127 · see citing works
An Evaluation of the Integration of Pharmacokinetic and Pharmacodynamic Principles in Clinical Drug Development
Reigner, B. G., Williams, P. E. O., Patel, I. H., Steimer, J., Peck, C. C., & van Brummelen, P. (1997) · Clinical Pharmacokinetics · doi:10.2165/00003088-199733020-00005 · Cited by 121 · see citing works
Untitled work
(1997) · PubMed · Cited by 121 · see citing works
Physiologic modeling of cyclosporin kinetics in rat and man
Bernareggi, A., & Rowland, M. (1991) · Journal of pharmacokinetics and biopharmaceutics · doi:10.1007/bf01062191 · Cited by 120 · see citing works
Development of a 7-Day, 96-Well Caco-2 Permeability Assay with High-Throughput Direct UV Compound Analysis
Alsenz, J., & Haenel, E. (2003) · Pharmaceutical Research · doi:10.1023/b:pham.0000008043.71001.43 · Cited by 110 · see citing works
The Use of Human Hepatocytes to Select Compounds Based on Their Expected Hepatic Extraction Ratios in Humans
Lavé, T., Dupin, S., Schmitt, C., Valles, B., Ubeaud, G., Chou, R. C., Jaeck, D., & Coassolo, P. (1997) · Pharmaceutical Research · doi:10.1023/a:1012036324237 · Cited by 106 · see citing works
Interspecies scaling: Predicting pharmacokinetic parameters of antiepileptic drugs in humans from animals with special emphasis on clearance
Mahmood, I., & Balian, J. D. (1996) · Journal of Pharmaceutical Sciences · doi:10.1021/js950400y · Cited by 105 · see citing works
A COMPREHENSIVE QUANTITATIVE AND QUALITATIVE EVALUATION OF EXTRAPOLATION OF INTRAVENOUS PHARMACOKINETIC PARAMETERS FROM RAT, DOG, AND MONKEY TO HUMANS. II. VOLUME OF DISTRIBUTION AND MEAN RESIDENCE TIME
Ward, K. W., & Smith, B. R. (2004) · Drug Metabolism and Disposition · doi:10.1124/dmd.32.6.612 · Cited by 105 · see citing works
Prediction of diazepam disposition in the rat and man by a physiologically based pharmacokinetic model
Igari, Y., Sugiyama, Y., Sawada, Y., Iga, T., & Hanano, M. (1983) · Journal of Pharmacokinetics and Biopharmaceutics · doi:10.1007/bf01059058 · Cited by 104 · see citing works
Prediction of the volumes of distribution of basic drugs in humans based on data from animals
Sawada, Y., Hanano, M., Sugiyama, Y., Harashima, H., & Iga, T. (1984) · Journal of pharmacokinetics and biopharmaceutics · doi:10.1007/bf01059554 · Cited by 94 · see citing works
Prediction of Hepatic Metabolic Clearance: Comparison and Assessment of Prediction Models
Zuegge, J., Schneider, G., Coassolo, P., & Lav??, T. (2001) · Clinical Pharmacokinetics · doi:10.2165/00003088-200140070-00006 · Cited by 92 · see citing works
Self-citation
Physiological pharmacokinetics of ethoxybenzamide based on biochemical data obtainedin vitro as well as on physiological data
Lin, J. H., Sugiyama, Y., Awazu, S., & Hanano, M. (1982) · Journal of Pharmacokinetics and Biopharmaceutics · doi:10.1007/bf01062546 · Cited by 92 · see citing works
Interspecies scaling of renally secreted drugs
Mahmood, I. (1998) · Life Sciences · doi:10.1016/s0024-3205(98)00525-6 · Cited by 88 · see citing works
Quantitative Structure-Pharmacokinetics Relationships: I. Development of a Whole-Body Physiologically Based Model to Characterize Changes in Pharmacokinetics Across a Homologous Series of Barbiturates in the Rat
Blakey, G. E., Nestorov, I. A., Arundel, P. A., Aarons, L. J., & Rowland, M. (1997) · Journal of Pharmacokinetics and Biopharmaceutics · doi:10.1023/a:1025771608474 · Cited by 85 · see citing works
Phosphatidylserine as a Determinant for the Tissue Distribution of Weakly Basic Drugs in Rats
Yata, N., Toyoda, T., Murakami, T., Nishiura, A., & Higashi, Y. (1990) · Pharmaceutical Research · doi:10.1023/a:1015935031933 · Cited by 78 · see citing works
Physiologically Based Pharmacokinetic (PBPK) Modeling of Disposition of Epiroprim in Humans
Luttringer, O., Theil, F., Poulin, P., Schmitt‐Hoffmann, A. H., Guentert, T. W., & Lavé, T. (2003) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.10461 · Cited by 75 · see citing works
Self-citation
Use of a Biophysical-Kinetic Model to Understand the Roles of Protein Binding and Membrane Partitioning on Passive Diffusion of Highly Lipophilic Molecules Across Cellular Barriers
Raub, T. J., Barsuhn, C. L., Williams, L. R., Decker, D. E., Sawada, G. A., & Ho, N. F. H. (1993) · Journal of drug targeting · doi:10.3109/10611869308996085 · Cited by 70 · see citing works
Increased Lipophilicity and Subsequent Cell Partitioning Decrease Passive Transcellular Diffusion of Novel, Highly Lipophilic Antioxidants
Sawada, G. A., Barsuhn, C. L., Lutzke, B. S., Houghton, M., Padbury, G. E., Ho, N. F. H., & Raub, T. J. (1999) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)38088-7 · Cited by 67 · see citing works
APPLICATION OF A GENERIC PHYSIOLOGICALLY BASED PHARMACOKINETIC MODEL TO THE ESTIMATION OF XENOBIOTIC LEVELS IN RAT PLASMA
Brightman, F. A., Leahy, D. E., Searle, G. E., & Thomas, S. (2005) · Drug Metabolism and Disposition · doi:10.1124/dmd.105.004804 · Cited by 67 · see citing works
Interspecies Pharmacokinetic Comparisons and Allometric Scaling of Napsagatran, a Low Molecular Weight Thrombin Inhibitor
Lavé, T., Portmann, R., Schenker, G., Gianni, A., Guenzi, A., Girometta, M. A., & Schmitt, M. (1999) · Journal of Pharmacy and Pharmacology · doi:10.1211/0022357991772006 · Cited by 57 · see citing works
Self-citation
APPLICATION OF A GENERIC PHYSIOLOGICALLY BASED PHARMACOKINETIC MODEL TO THE ESTIMATION OF XENOBIOTIC LEVELS IN HUMAN PLASMA
Brightman, F. A., Leahy, D. E., Searle, G. E., & Thomas, S. (2005) · Drug Metabolism and Disposition · doi:10.1124/dmd.105.004838 · Cited by 53 · see citing works
Excretion of Drugs in Bile
Smith, R. L. (1971) · Springer eBooks · doi:10.1007/978-3-642-65052-9_19 · Cited by 46 · see citing works
Anatomical and physiological differences betweenvarious species used in studies on the pharmacokinetics and toxicology of xenobiotics. A review ofliterature
de, Z. L., Cjm, R., Ajam, S., Welink, J., & van, E. J. (1999) · Cited by 44 · see citing works
Critique of Prospective Allometric Scaling: Does the Emperor Have Clothes?
Bonate, P. L., & Howard, D. R. (2000) · The Journal of Clinical Pharmacology · doi:10.1177/00912700022009017 · Cited by 43 · see citing works
The excretory function of bile: The elimination of drugs and toxic substances in bile
(1974) · Food and Cosmetics Toxicology · doi:10.1016/0015-6264(74)90265-x · Cited by 40 · see citing works
Predicting human pharmacokinetics from preclinical data.
Poggesi, I. (2004) · PubMed · Cited by 39 · see citing works
Comparative Pharmacokinetics and Interspecies Scaling of Amphotericin B in Several Mammalian Species
Hutchaleelaha, A., Chow, H.-H., & Mayersohn, M. (1997) · Journal of Pharmacy and Pharmacology · doi:10.1111/j.2042-7158.1997.tb06775.x · Cited by 39 · see citing works
Prospective Allometric Scaling: Does the Emperor Have Clothes?
Bonate, P. L., & Howard, D. R. (2000) · The Journal of Clinical Pharmacology · doi:10.1177/009127000004000601 · Cited by 36 · see citing works
Animal Pharmacokinetics and Interspecies Scaling from Animals to Man of Lamifiban, a New Platelet Aggregation Inhibitor
Lavé, T., Saner, A., Coassolo, P., Brandt, R. D., Schmitt‐Hoffmann, A. H., & Chou, R. C. (1996) · Journal of Pharmacy and Pharmacology · doi:10.1111/j.2042-7158.1996.tb05976.x · Cited by 36 · see citing works
Self-citation
Incorporating Measures of Variability and Uncertainty into the Prediction of in Vivo Hepatic Clearance from in Vitro Data
Nestorov, I. A., Gueorguieva, I., Jones, H. M., Houston, B., & Rowland, M. (2002) · Drug Metabolism and Disposition · doi:10.1124/dmd.30.3.276 · Cited by 27 · see citing works
Self-citation
Effect of fat tissue volume on the distribution kinetics of biperiden as a function of age in rats.
Yokogawa, K., Nakashima, E., & Ichimura, F. (1990) · Drug Metabolism and Disposition · doi:10.1016/s0090-9556(25)07615-9 · Cited by 24 · see citing works
Prediction of the pharmacokinetic parameters of reduced- dolasetron in man usingin vitro-in vivoand interspecies allometric scaling
Ducray, P. S., & DOW*, J. (1997) · Xenobiotica · doi:10.1080/004982597240686 · Cited by 19 · see citing works
QUANTITATIVE PREDICTION OF THE IN VIVO INHIBITION OF DIAZEPAM METABOLISM BY OMEPRAZOLE USING RAT LIVER MICROSOMES AND HEPATOCYTES
Jones, H. M., Hallifax, D., & Houston, J. B. (2004) · Drug Metabolism and Disposition · doi:10.1124/dmd.32.5.572 · Cited by 17 · see citing works
Self-citation
ChemInform Abstract: Extrapolation of Toxicological and Pharmacological Data from Animals to Humans
Chappell, W. R., & Mordenti, J. J. (1991) · ChemInform · doi:10.1002/chin.199135330 · Cited by 14 · see citing works
Interspecies pharmacokinetic scaling of metazosin, a novel alpha‐adrenergic antagonist
Lapka, R., Rejholec, V., Sechser, T., Peterková, M., & Šmíd, M. (1989) · Biopharmaceutics & Drug Disposition · doi:10.1002/bdd.2510100607 · Cited by 12 · see citing works
Untitled work
Taillefer (2000) · doi:10.1002/(sici)1520-6017(200001)89:1

Flagged first, then by citations

Sorted by citations

Mechanism-Based Concepts of Size and Maturity in Pharmacokinetics
Anderson, B. J., & Holford, N. H. G. (2007) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.48.113006.094708 · Cited by 1,129 · see citing works
Physiologically-Based Pharmacokinetics in Drug Development and Regulatory Science
Rowland, M., Peck, C., & Tucker, G. (2011) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010510-100540 · Cited by 662 · see citing works
Basic Concepts in Physiologically Based Pharmacokinetic Modeling in Drug Discovery and Development
Jones, H., & Rowland‐Yeo, K. (2013) · CPT: Pharmacometrics & Systems Pharmacology · doi:10.1038/psp.2013.41 · Cited by 626 · see citing works
Self-citation
To Scale or Not to Scale: The Principles of Dose Extrapolation
Sharma, V., & McNeill, J. H. (2009) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2009.00267.x · Cited by 544 · see citing works
The Simcyp <sup>®</sup> Population-based ADME Simulator
Jamei, M., Marciniak, S., Feng, K., Barnett, A., Tucker, G., & Rostami-Hodjegan, A. (2009) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425250802691074 · Cited by 533 · see citing works
Physiologically based pharmacokinetic modeling in drug discovery and development: A pharmaceutical industry perspective
Jones, H., Chen, Y., Gibson, C., Heimbach, T., Parrott, N., Peters, S., Snoeys, J., Upreti, V., Zheng, M., & Hall, S. (2015) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.37 · Cited by 488 · see citing works
Self-citation
Applied Concepts in PBPK Modeling: How to Build a PBPK/PD Model
Kuepfer, L., Niederalt, C., Wendl, T., Schlender, J., Willmann, S., Lippert, J., Block, M., Eissing, T., & Teutonico, D. (2016) · CPT: Pharmacometrics & Systems Pharmacology · doi:10.1002/psp4.12134 · Cited by 425 · see citing works
Mechanistic Approaches to Volume of Distribution Predictions: Understanding the Processes
Rodgers, T., & Rowland, M. (2007) · Pharmaceutical Research · doi:10.1007/s11095-006-9210-3 · Cited by 420 · see citing works
PBPK modeling and simulation in drug research and development
Zhuang, X., & Lu, C. (2016) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2016.04.004 · Cited by 411 · see citing works
Physiologically Based Pharmacokinetic Modeling to Predict Transporter-Mediated Clearance and Distribution of Pravastatin in Humans
Watanabe, T., Kusuhara, H., Maeda, K., Shitara, Y., & Sugiyama, Y. (2008) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.108.146647 · Cited by 351 · see citing works
Pharmacokinetics
Fan, J., & de Lannoy, I. A. M. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.09.007 · Cited by 309 · see citing works
Prediction of Human Pharmacokinetics from Preclinical Information: Comparative Accuracy of Quantitative Prediction Approaches
Hosea, N. A., Collard, W. T., Cole, S., Maurer, T. S., Fang, R. X., Jones, H., Kakar, S. M., Nakai, Y., Smith, B. J., Webster, R., et al. (2009) · The Journal of Clinical Pharmacology · doi:10.1177/0091270009333209 · Cited by 300 · see citing works
Self-citation
Prediction of Drug-Drug Interactions with Bupropion and Its Metabolites as CYP2D6 Inhibitors Using a Physiologically-Based Pharmacokinetic Model
Xue, C., Zhang, X., & Cai, W. (2017) · Pharmaceutics · doi:10.3390/pharmaceutics10010001 · Cited by 291 · see citing works
Prediction of human pharmacokinetics using physiologically based modeling: a retrospective analysis of 26 clinically tested drugs
De Buck, S. S., Sinha, V. K., Fenu, L. A., Nijsen, M. J., Mackie, C. E., & Gilissen, R. A. H. J. (2007) · Drug Metabolism and Disposition · doi:10.1124/dmd.107.015644 · Cited by 256 · see citing works
Mechanistic Pharmacokinetic Modeling for the Prediction of Transporter-Mediated Disposition in Humans from Sandwich Culture Human Hepatocyte Data
Jones, H. M., Barton, H. A., Lai, Y., Bi, Y., Kimoto, E., Kempshall, S., Tate, S. C., El‐Kattan, A. F., Houston, J. B., Galetin, A., et al. (2012) · Drug Metabolism and Disposition · doi:10.1124/dmd.111.042994 · Cited by 243 · see citing works
Self-citation
Genetic polymorphisms of uptake (OATP1B1, 1B3) and efflux (MRP2, BCRP) transporters: implications for inter-individual differences in the pharmacokinetics and pharmacodynamics of statins and other clinically relevant drugs
Ieiri, I., Higuchi, S., & Sugiyama, Y. (2009) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425250902976854 · Cited by 211 · see citing works
Modelling and PBPK Simulation in Drug Discovery
Jones, H., Gardner, I., & Watson, K. J. (2009) · AAPS Journal · doi:10.1208/s12248-009-9088-1 · Cited by 213 · see citing works
Self-citation
Safety evaluation of superabsorbent baby diapers
Kosemund, K., Schlatter, H., Ochsenhirt, J. L., Krause, E. L., Marsman, D. S., & Erasala, G. N. (2008) · Regulatory Toxicology and Pharmacology · doi:10.1016/j.yrtph.2008.10.005 · Cited by 196 · see citing works
Whole-body physiologically based pharmacokinetic models
Nestorov, I. A. (2007) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.3.2.235 · Cited by 188 · see citing works
Human Ontogeny of Drug Transporters: Review and Recommendations of the Pediatric Transporter Working Group
Brouwer, K. L. R., Aleksunes, L. M., Brandys, B., Giacoia, G. P., Knipp, G. T., Lukacova, V., Meibohm, B., Nigám, S. K., Rieder, M. J., de Wildt, S. N., et al. (2015) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.176 · Cited by 185 · see citing works
Non-invasive Systemic Drug Delivery: Developability Considerations for Alternate Routes of Administration
Mathias, N. R., & Hussain, M. A. (2009) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.21793 · Cited by 183 · see citing works
PHRMA CPCDC initiative on predictive models of human pharmacokinetics, part 5: Prediction of plasma concentration–time profiles in human by using the physiologically‐based pharmacokinetic modeling approach
Poulin, P., Jones, R. D. O., Jones, H. M., Gibson, C. R., Rowland, M., Chien, J. Y., Ring, B. J., Adkison, K. K., Ku, M. S., He, H., et al. (2011) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.22550 · Cited by 174 · see citing works
Self-citation
Predicting Oral Drug Absorption: Mini Review on Physiologically-Based Pharmacokinetic Models
Lin, L., & Wong, H. (2017) · Pharmaceutics · doi:10.3390/pharmaceutics9040041 · Cited by 172 · see citing works
Towards Prediction of In Vivo Intestinal Absorption Using a 96-Well Caco-2 Assay
Skolnik, S. M., Lin, X., Wang, J., Chen, X.-H., He, T., & Zhang, B. (2010) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.22080 · Cited by 154 · see citing works
Food Effects on Oral Drug Absorption: Application of Physiologically-Based Pharmacokinetic Modeling as a Predictive Tool
Cheng, L., & Wong, H. (2020) · Pharmaceutics · doi:10.3390/pharmaceutics12070672 · Cited by 154 · see citing works
Whole body physiologically-based pharmacokinetic models: their use in clinical drug development
Edginton, A. N., Theil, F., Schmitt, W., & Willmann, S. (2008) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.4.9.1143 · Cited by 154 · see citing works
Predicting Pharmacokinetics of Drugs Using Physiologically Based Modeling—Application to Food Effects
Parrott, N. J., Lukacova, V., Fraczkiewicz, G., & Bolger, M. B. (2009) · The AAPS Journal · doi:10.1208/s12248-008-9079-7 · Cited by 150 · see citing works
Self-citation
PBTK modelling platforms and parameter estimation tools to enable animal-free risk assessment
Bessems, J. G. M., Loizou, G. D., Krishnan, K., M.A., H. J. C. I., Bernasconi, C., Bois, F. Y., Coecke, S., Collnot, E.-M., Diembeck, W., Farcal, L. R., et al. (2013) · Regulatory Toxicology and Pharmacology · doi:10.1016/j.yrtph.2013.11.008 · Cited by 152 · see citing works
Predicting Pharmacokinetic Food Effects Using Biorelevant Solubility Media and Physiologically Based Modelling
Jones, H. M., Parrott, N. J., Ohlenbusch, G., & Lav, T. (2006) · Clinical Pharmacokinetics · doi:10.2165/00003088-200645120-00006 · Cited by 149 · see citing works
Self-citation
Evaluation of a Generic Physiologically Based Pharmacokinetic Model for Lineshape Analysis
Peters, S. A. (2008) · Clinical Pharmacokinetics · doi:10.2165/00003088-200847040-00004 · Cited by 148 · see citing works
Physiologically Based Pharmacokinetic Modelling for First-In-Human Predictions: An Updated Model Building Strategy Illustrated with Challenging Industry Case Studies
Miller, N. A., Reddy, M. B., Heikkinen, A. T., Lukacova, V., & Parrott, N. (2019) · Clinical Pharmacokinetics · doi:10.1007/s40262-019-00741-9 · Cited by 142 · see citing works
Self-citation
PhRMA CPCDC initiative on predictive models of human pharmacokinetics, part 2: Comparative assessment of prediction methods of human volume of distribution
Jones, R. D. O., Jones, H. M., Rowland, M., Gibson, C. R., Yates, J. W. T., Chien, J. Y., Ring, B. J., Adkison, K. K., Ku, M. S., He, H., et al. (2011) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.22553 · Cited by 142 · see citing works
Self-citation
Dosing in Children: A Critical Review of the Pharmacokinetic Allometric Scaling and Modelling Approaches in Paediatric Drug Development and Clinical Settings
Mahmood, I. (2014) · Clinical Pharmacokinetics · doi:10.1007/s40262-014-0134-5 · Cited by 141 · see citing works
Applications of Human Pharmacokinetic Prediction in First-in-Human Dose Estimation
Zou, P., Yu, Y., Zheng, N., Yang, Y., Paholak, H. J., Yu, L. X., & Sun, D. (2012) · The AAPS Journal · doi:10.1208/s12248-012-9332-y · Cited by 138 · see citing works
Physiologically based pharmacokinetics (PBPK)
Espié, P., Tytgat, D., Sargentini-Maier, M.-L., Poggesi, I., & Watelet, J. (2009) · Drug Metabolism Reviews · doi:10.1080/10837450902891360 · Cited by 138 · see citing works
Toward Predictive Models for Drug-Induced Liver Injury in Humans: Are we There Yet?
Chen, M., Bişğin, H., Tong, L., Hong, H., Fang, H., Borlak, J. T., & Tong, W. (2014) · Biomarkers in Medicine · doi:10.2217/bmm.13.146 · Cited by 136 · see citing works
Utility of Physiologically Based Absorption Modeling in Implementing Quality by Design in Drug Development
Zhang, X., Lionberger, R. A., Davit, B. M., & Yu, L. X. (2011) · The AAPS Journal · doi:10.1208/s12248-010-9250-9 · Cited by 129 · see citing works
Introduction to computational oral absorption simulation
Sugano, K. (2009) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425250902835506 · Cited by 129 · see citing works
Lipophilicity and biomimetic properties measured by HPLC to support drug discovery
Valko, K. L. (2016) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2016.04.009 · Cited by 129 · see citing works
Applications of Physiologically Based Absorption Models in Drug Discovery and Development
Parrott, N. J., & Lavé, T. (2008) · Molecular Pharmaceutics · doi:10.1021/mp8000155 · Cited by 123 · see citing works
Self-citation
Advancing Predictions of Tissue and Intracellular Drug Concentrations Using In Vitro, Imaging and Physiologically Based Pharmacokinetic Modeling Approaches
Guo, Y., Chu, X., Parrott, N. J., Brouwer, K. L. R., Hsu, V., Nagar, S., Matsson, P., Sharma, P. K., Snoeys, J., Sugiyama, Y., et al. (2018) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.1183 · Cited by 122 · see citing works
Self-citation
Challenges and opportunities with modelling and simulation in drug discovery and drug development
Lavé, T., Parrott, N., Grimm, H. P., Fleury, A., & Reddy, M. (2007) · Xenobiotica · doi:10.1080/00498250701534885 · Cited by 115 · see citing works
Self-citation
Development of a Physiologically Based Model for Oseltamivir and Simulation of Pharmacokinetics in Neonates and Infants
Parrott, N. J., Davies, B., Hoffmann, G., Koerner, A., Lavé, T., Prinssen, E. P. M., Theogaraj, E., & Singer, T. (2011) · Clinical Pharmacokinetics · doi:10.2165/11592640-000000000-00000 · Cited by 114 · see citing works
Self-citation
Application of IVIVE and PBPK modeling in prospective prediction of clinical pharmacokinetics: strategy and approach during the drug discovery phase with four case studies
Chen, Y., Jin, J. Y., Mukadam, S., Malhi, V., & Kenny, J. R. (2012) · Biopharmaceutics & Drug Disposition · doi:10.1002/bdd.1769 · Cited by 113 · see citing works
Pharmacokinetics and pharmacodynamics of ponesimod, a selective S1P1 receptor modulator, in the first‐in‐human study
Brossard, P., Derendorf, H., Xu, J., Maatouk, H., Halabi, A., & Dingemanse, J. (2013) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.12129 · Cited by 111 · see citing works
Cell cultures in drug discovery and development: The need of reliable in vitro-in vivo extrapolation for pharmacodynamics and pharmacokinetics assessment
Jaroch, K., Jaroch, A., & Bojko, B. (2017) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2017.07.023 · Cited by 110 · see citing works
Simulation of Human Intravenous and Oral Pharmacokinetics of 21 Diverse Compounds Using Physiologically Based Pharmacokinetic Modelling
Jones, H. M., Gardner, I. B., Collard, W. T., Stanley, P. J., Oxley, P., Hosea, N. A., Plowchalk, D., Gernhardt, S., Lin, J., Dickins, M., et al. (2011) · Clinical Pharmacokinetics · doi:10.2165/11539680-000000000-00000 · Cited by 110 · see citing works
Self-citation
Application of physiologically based pharmacokinetic modeling and clearance concept to drugs showing transporter-mediated distribution and clearance in humans
Watanabe, T., Kusuhara, H., & Sugiyama, Y. (2010) · Journal of Pharmacokinetics and Pharmacodynamics · doi:10.1007/s10928-010-9176-y · Cited by 109 · see citing works
Dissolution and Translational Modeling Strategies Toward Establishing an In Vitro-In Vivo Link—a Workshop Summary Report
Heimbach, T., Suarez‐Sharp, S., Kakhi, M., Holmstock, N., Olivares-Morales, A., Pepin, X. J. H., Sjögren, E., Tsakalozou, E., Seo, P., Li, M., et al. (2019) · The AAPS Journal · doi:10.1208/s12248-019-0298-x · Cited by 109 · see citing works
Dose Selection Based on Physiologically Based Pharmacokinetic (PBPK) Approaches
Jones, H. M., Mayawala, K., & Poulin, P. (2012) · The AAPS Journal · doi:10.1208/s12248-012-9446-2 · Cited by 107 · see citing works
Self-citation
Toward an improved prediction of humanin vivobrain penetration
Summerfield, S. G., Lucas, A. J., Porter, R. A., Jeffrey, P., Gunn, R. N., Read, K. R., Stevens, A. J., Metcalf, A., Osuna, M. C., Kilford, P. J., et al. (2008) · Xenobiotica · doi:10.1080/00498250802499459 · Cited by 105 · see citing works
Physiologically based pharmacokinetic (PBPK) modelling tools: how to fit with our needs?
Bouzom, F., Ball, K., Perdaems, N., & Walther, B. (2012) · Biopharmaceutics & Drug Disposition · doi:10.1002/bdd.1767 · Cited by 99 · see citing works
Application of PBPK modelling in drug discovery and development at Pfizer
Jones, H. M., Dickins, M., Youdim, K. A., Gosset, J. R., Attkins, N. J., Hay, T. L., Gurrell, I. K., Logan, Y. R., Bungay, P. J., Jones, B., et al. (2011) · Xenobiotica · doi:10.3109/00498254.2011.627477 · Cited by 98 · see citing works
Self-citation
The pig as a preclinical model for predicting oral bioavailability and in vivo performance of pharmaceutical oral dosage forms: a PEARRL review
Henze, L. J., Koehl, N. J., O’Shea, J. P., Kostewicz, E. S., Holm, R., & Griffin, B. T. (2018) · Journal of Pharmacy and Pharmacology · doi:10.1111/jphp.12912 · Cited by 94 · see citing works
A Physiologically Based Pharmacokinetic Model of the Minipig: Data Compilation and Model Implementation
Suenderhauf, C., & Parrott, N. J. (2012) · Pharmaceutical Research · doi:10.1007/s11095-012-0911-5 · Cited by 93 · see citing works
Self-citation
The Prediction of Drug Metabolism, Tissue Distribution, and Bioavailability of 50 Structurally Diverse Compounds in Rat Using Mechanism-Based Absorption, Distribution, and Metabolism Prediction Tools
Buck, S. S. D., Sinha, V. K., Fenu, L. A., Gilissen, R., Mackie, C. E., & Nijsen, M. (2007) · Drug Metabolism and Disposition · doi:10.1124/dmd.106.014027 · Cited by 92 · see citing works
Prediction of drug–drug interaction potential using physiologically based pharmacokinetic modeling
Min, J. S., & Bae, S. K. (2017) · Archives of Pharmacal Research · doi:10.1007/s12272-017-0976-0 · Cited by 88 · see citing works
Quantitative structure–pharmacokinetic/pharmacodynamic relationships
Mager, D. E. (2006) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2006.08.002 · Cited by 85 · see citing works
On the anticipation of the human dose in first-in-man trials from preclinical and prior clinical information in early drug development
Lowe, P. J., Hijazi, Y., Luttringer, O., Yin, H., Sarangapani, R., & Howard, D. (2007) · Xenobiotica · doi:10.1080/00498250701648008 · Cited by 82 · see citing works
Prediction of pharmacokinetic profile of valsartan in human based on in vitro uptake transport data
Poirier, A., Cascais, A., Funk, C., & Lavé, T. (2009) · Journal of Pharmacokinetics and Pharmacodynamics · doi:10.1007/s10928-009-9139-3 · Cited by 80 · see citing works
Self-citation
Application of PBPK modeling to predict human intestinal metabolism of CYP3A substrates – An evaluation and case study using GastroPlus™
Heikkinen, A. T., Baneyx, G., Caruso, A., & Parrott, N. (2012) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2012.06.013 · Cited by 76 · see citing works
Self-citation
A “middle-out” approach to human pharmacokinetic predictions for OATP substrates using physiologically-based pharmacokinetic modeling
Li, R., Barton, H. A., Yates, P. D., Ghosh, A., Wolford, A. C., Riccardi, K. A., & Maurer, T. S. (2014) · Journal of Pharmacokinetics and Pharmacodynamics · doi:10.1007/s10928-014-9357-1 · Cited by 75 · see citing works
Physiologically based pharmacokinetic modeling of CYP3A4 induction by rifampicin in human: Influence of time between substrate and inducer administration
Baneyx, G., Parrott, N. J., Meille, C., Iliadis, A., & Lavé, T. (2014) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2014.02.002 · Cited by 77 · see citing works
Self-citation
Developing Exposure/Response Models for Anticancer Drug Treatment: Special Considerations
Mould, D., Walz, A., Lavé, T., Gibbs, J., & Frame, B. (2015) · CPT Pharmacometrics & Systems Pharmacology · doi:10.1002/psp4.16 · Cited by 75 · see citing works
Self-citation
Development of a Web-Based Toolbox to Support Quantitative In-Vitro-to-In-Vivo Extrapolations (QIVIVE) within Nonanimal Testing Strategies
Punt, A., Pinckaers, N. E. T., Peijnenburg, A., & Louisse, J. (2020) · Chemical Research in Toxicology · doi:10.1021/acs.chemrestox.0c00307 · Cited by 73 · see citing works
Preclinical Prediction of Human Brain Target Site Concentrations: Considerations in Extrapolating to the Clinical Setting
Westerhout, J., Danhof, M., & de Lange, E. C. M. (2011) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.22604 · Cited by 72 · see citing works
Physiologically-based Kinetic Modelling (PBK Modelling): Meeting the 3Rs Agenda
d’Yvoire, M. B., Prieto, P., Blaauboer, B. J., Bois, F. Y., Boobis, A. R., Brochot, C., Coecke, S., Freidig, A. P., Gundert‐Remy, U., Härtung, T., et al. (2007) · Alternatives to Laboratory Animals · doi:10.1177/026119290703500606 · Cited by 72 · see citing works
Self-citation
Pharmacometrics at FDA: Evolution and Impact on Decisions
Powell, J. R., & Gobburu, J. V. S. (2007) · Clinical Pharmacology & Therapeutics · doi:10.1038/sj.clpt.6100234 · Cited by 72 · see citing works
Prediction of Crizotinib-Midazolam Interaction Using the Simcyp Population-Based Simulator: Comparison of CYP3A Time-Dependent Inhibition between Human Liver Microsomes versus Hepatocytes
Mao, J., Johnson, T. R., Shen, Z., & Yamazaki, S. (2012) · Drug Metabolism and Disposition · doi:10.1124/dmd.112.049114 · Cited by 71 · see citing works
Simulation of the pharmacokinetics of bisoprolol in healthy adults and patients with impaired renal function using whole-body physiologically based pharmacokinetic modeling
Li, G., Wang, K., Chen, R., Hao-ru, Z., Yang, J., & Zheng, Q. (2012) · Acta Pharmacologica Sinica · doi:10.1038/aps.2012.103 · Cited by 70 · see citing works
Influence of different proton pump inhibitors on the pharmacokinetics of voriconazole
Qi, F., Zhu, L., Li, N., Ge, T., Xu, G., & Liao, S. (2017) · International Journal of Antimicrobial Agents · doi:10.1016/j.ijantimicag.2016.11.025 · Cited by 69 · see citing works
Lumping of physiologically-based pharmacokinetic models and a mechanistic derivation of classical compartmental models
Pilari, S., & Huisinga, W. (2010) · Journal of Pharmacokinetics and Pharmacodynamics · doi:10.1007/s10928-010-9165-1 · Cited by 67 · see citing works
Physiologically Based Predictions of the Impact of Inhibition of Intestinal and Hepatic Metabolism on Human Pharmacokinetics of CYP3A Substrates
Fenneteau, F., Poulin, P., & Nekka, F. (2009) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.21802 · Cited by 66 · see citing works
Predicting Pharmacokinetic Profiles Using <i>in Silico</i> Derived Parameters
Hosea, N. A., & Jones, H. M. (2013) · Molecular Pharmaceutics · doi:10.1021/mp300482w · Cited by 65 · see citing works
Self-citation
Predictions of Metabolic Drug-Drug Interactions Using Physiologically Based Modelling
Perdaems, N., Blasco, H., Vinson, C., Chenel, M., Whalley, S., Cazade, F., & Bouzom, F. (2010) · Clinical Pharmacokinetics · doi:10.2165/11318130-000000000-00000 · Cited by 59 · see citing works
PhRMA CPCDC Initiative on Predictive Models of Human Pharmacokinetics, Part 1: Goals, Properties of the Phrma Dataset, and Comparison with Literature Datasets
Poulin, P., Jones, H. M., Jones, R. D. O., Yates, J. W. T., Gibson, C. R., Chien, J. Y., Ring, B. J., Adkison, K. K., He, H., Vuppugalla, R., et al. (2011) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.22554 · Cited by 62 · see citing works
Self-citation
A testing strategy to predict risk for drug-induced liver injury in humans using high-content screen assays and the ‘rule-of-two’ model
Chen, M., Tung, C.-W., Shi, Q., Guo, L., Shi, L. M., Fang, H., Borlak, J. T., & Tong, W. (2014) · Archives of Toxicology · doi:10.1007/s00204-014-1276-9 · Cited by 62 · see citing works
PBPK modeling of intestinal and liver enzymes and transporters in drug absorption and sequential metabolism.
Fan, J.-H., Chen, S., Chow, E., & Pang, K. (2010) · Current drug metabolism · doi:10.2174/138920010794328931 · Cited by 59 · see citing works
Prediction of Oral Pharmacokinetics of cMet Kinase Inhibitors in Humans: Physiologically Based Pharmacokinetic Model Versus Traditional One-Compartment Model
Yamazaki, S., Skaptason, J., Romero, D., Vekich, S., Jones, H., Tan, W.-W., Wilner, K., & Koudriakova, T. (2011) · Drug Metabolism And Disposition · doi:10.1124/dmd.110.035857 · Cited by 69 · see citing works
Self-citation
Mechanistic Modeling of Hepatic Transport from Cells to Whole Body: Application to Napsagatran and Fexofenadine
Poirier, A., Funk, C., Scherrmann, J., & Lavé, T. (2009) · Molecular Pharmaceutics · doi:10.1021/mp8002495 · Cited by 61 · see citing works
Self-citation
Gut Wall Metabolism. Application of Pre-Clinical Models for the Prediction of Human Drug Absorption and First-Pass Elimination
Jones, C. R., Hatley, O. J. D., Ungell, A.-L. B., Hilgendorf, C., Peters, S. A., & Rostami‐Hodjegan, A. (2016) · The AAPS Journal · doi:10.1208/s12248-016-9889-y · Cited by 61 · see citing works
Evaluation of the Success of High-Throughput Physiologically Based Pharmacokinetic (HT-PBPK) Modeling Predictions to Inform Early Drug Discovery
Naga, D., Parrott, N. J., Ecker, G. F., & Olivares‐Morales, A. (2022) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.2c00040 · Cited by 62 · see citing works
Self-citation
Pre-clinical pharmacokinetics of UK-453,061, a novel non-nucleoside reverse transcriptase inhibitor (NNRTI), and use of in silico physiologically based prediction tools to predict the oral pharmacokinetics of UK-453,061 in man
Allan, G. A., Davis, J. D., Dickins, M., Gardner, I., Jenkins, T. M., Jones, H. M., Webster, R., & Westgate, H. (2008) · Xenobiotica · doi:10.1080/00498250802069088 · Cited by 60 · see citing works
Self-citation
PhRMA CPCDC initiative on predictive models of human pharmacokinetics, part 4: Prediction of plasma concentration–time profiles in human from in vivo preclinical data by using the Wajima approach
Vuppugalla, R., Marathe, P., He, H., Jones, R. D. O., Yates, J. W. T., Jones, H. M., Gibson, C. R., Chien, J. Y., Ring, B. J., Adkison, K. K., et al. (2011) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.22551 · Cited by 60 · see citing works
Self-citation
A Physiologically Based Pharmacokinetic Drug–Disease Model to Predict Carvedilol Exposure in Adult and Paediatric Heart Failure Patients by Incorporating Pathophysiological Changes in Hepatic and Renal Blood Flows
Rasool, M. F., Khalil, F., & Läer, S. (2015) · Clinical Pharmacokinetics · doi:10.1007/s40262-015-0253-7 · Cited by 59 · see citing works
Physiologically based approaches towards the prediction of pharmacokinetics:in vitro–in vivoextrapolation
Buck, S. S. D., & Mackie, C. E. (2007) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.3.6.865 · Cited by 58 · see citing works
Role of transport proteins in drug discovery and development: a pharmaceutical perspective
Ayrton, A. D., & Morgan, P. (2008) · Xenobiotica · doi:10.1080/00498250801923855 · Cited by 58 · see citing works
Quantitative ADME Proteomics – CYP and UGT Enzymes in the Beagle Dog Liver and Intestine
Heikkinen, A. T., Friedlein, A., Matondo, M., Hatley, O. J. D., Petsalo, A., Juvonen, R. O., Galetin, A., Rostami‐Hodjegan, A., Aebersold, R. H., Lamerz, J., et al. (2014) · Pharmaceutical Research · doi:10.1007/s11095-014-1446-8 · Cited by 56 · see citing works
Self-citation
Pharmacokinetic predictions in children by using the physiologically based pharmacokinetic modelling
Bouzom, F., & Walther, B. (2008) · Fundamental and Clinical Pharmacology · doi:10.1111/j.1472-8206.2008.00648.x · Cited by 55 · see citing works
Prediction of Drug Tissue to Plasma Concentration Ratios Using a Measured Volume of Distribution in Combination With Lipophilicity
Jansson‐Löfmark, R., Bredberg, U., & Ashton, M. (2007) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.21130 · Cited by 53 · see citing works
The evolution of the OATP hepatic uptake transport protein family in DMPK sciences: from obscure liver transporters to key determinants of hepatobiliary clearance
Fenner, K. S., Jones, H. M., Ullah, M., Kempshall, S., Dickins, M., Lai, Y., Morgan, P., & Barton, H. A. (2011) · Xenobiotica · doi:10.3109/00498254.2011.626464 · Cited by 53 · see citing works
Self-citation
Human clearance prediction: shifting the paradigm
Lavé, T., Chapman, K. L., Goldsmith, P., & Rowland, M. (2009) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425250903099649 · Cited by 51 · see citing works
Self-citation
Predicting Oral Clearance in Humans
Sinha, V. K., Buck, S. S. D., Fenu, L. A., Smit, J. W., Nijsen, M., Gilissen, R., Peer, A. V., Lavrijsen, K., & Mackie, C. E. (2008) · Clinical Pharmacokinetics · doi:10.2165/00003088-200847010-00004 · Cited by 49 · see citing works
Development of a Unified Dissolution and Precipitation Model and Its Use for the Prediction of Oral Drug Absorption
Jakubiak, P., Wagner, B., Grimm, H. P., Petrig-Schaffland, J., Schuler, F., & Alvarez‐Sánchez, R. (2015) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.5b00808 · Cited by 49 · see citing works
Formed and preformed metabolites: facts and comparisons
Pang, K., Morris, M., & Sun, H. (2008) · The Journal of pharmacy and pharmacology · doi:10.1211/jpp.60.10.0001 · Cited by 45 · see citing works
Differences in Food Effects for 2 Weak Bases With Similar BCS Drug-Related Properties: What Is Happening in the Intestinal Lumen?
Cristofoletti, R., Patel, N., & Dressman, J. (2016) · Journal of Pharmacy and Science · doi:10.1016/j.xphs.2015.11.033 · Cited by 46 · see citing works
A Physiologically‐Based Pharmacokinetic Model for the Prediction of Monoclonal Antibody Pharmacokinetics From In Vitro Data
Jones, H. M., Zhang, Z., Jasper, P., Luo, H., Avery, L. B., King, L. E., Neubert, H., Barton, H. A., Betts, A. M., & Webster, R. (2019) · CPT Pharmacometrics & Systems Pharmacology · doi:10.1002/psp4.12461 · Cited by 48 · see citing works
Self-citation
Physiologically Based Pharmacokinetic Modeling
M.A., H. J. C. I., Reddy, M. B., Lavé, T., & Andersen, M. E. (2010) · Pharmaceutical Sciences Encyclopedia · doi:10.1002/9780470571224.pse065 · Cited by 47 · see citing works
Self-citation
Novel in vitro and mathematical models for the prediction of chemical toxicity
Williams, D. P., Shipley, R. J., Ellis, M. J., Webb, S., Ward, J., Gardner, I. B., & Creton, S. K. (2012) · Toxicology Research · doi:10.1039/c2tx20031g · Cited by 47 · see citing works
Physiologically Based Pharmacokinetic Prediction of Telmisartan in Human
Li, R., Ghosh, A., Maurer, T. S., Kimoto, E., & Barton, H. A. (2014) · Drug Metabolism and Disposition · doi:10.1124/dmd.114.058461 · Cited by 44 · see citing works

Prediction of human pharmacokinetics using physiologically based modeling: a retrospective analysis of 26 clinically tested drugs
De Buck, S. S., Sinha, V. K., Fenu, L. A., Nijsen, M. J., Mackie, C. E., & Gilissen, R. A. H. J. (2007) · Drug Metabolism and Disposition · doi:10.1124/dmd.107.015644 · Cited by 256 · see citing works
PHRMA CPCDC initiative on predictive models of human pharmacokinetics, part 5: Prediction of plasma concentration–time profiles in human by using the physiologically‐based pharmacokinetic modeling approach
Poulin, P., Jones, R. D. O., Jones, H. M., Gibson, C. R., Rowland, M., Chien, J. Y., Ring, B. J., Adkison, K. K., Ku, M. S., He, H., et al. (2011) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.22550 · Cited by 174 · see citing works
Self-citation
Successful Prediction of Human Pharmacokinetics by Improving Calculation Processes of Physiologically Based Pharmacokinetic Approach.
Mayumi, K., Ohnishi, S., & Hasegawa, H. (2019) · Journal of Pharmacy and Science · doi:10.1016/j.xphs.2019.03.002 · Cited by 10 · see citing works
Simulation of Human Intravenous and Oral Pharmacokinetics of 21 Diverse Compounds Using Physiologically Based Pharmacokinetic Modelling
Jones, H. M., Gardner, I. B., Collard, W. T., Stanley, P. J., Oxley, P., Hosea, N. A., Plowchalk, D., Gernhardt, S., Lin, J., Dickins, M., et al. (2011) · Clinical Pharmacokinetics · doi:10.2165/11539680-000000000-00000 · Cited by 110 · see citing works
Self-citation
A novel physiologically based pharmacokinetics (PBPK) approach for human PK prediction
Mayumi, K., Matsuzaki, T., Funaki, S., Sakamoto, S. X., Ohnishi, S., & Hasegawa, H. (2018) · Drug Metabolism and Pharmacokinetics · doi:10.1016/j.dmpk.2017.11.280

Authors: Jones, H. M., Parrott, N., Jorga, K., & Lav??, T.
Affiliations: F. Hoffmann-La Roche AG (CH)
Corresponding author: Jones, Hannah M
ORCID: Jones, Hannah M
Parrott, Neil
Venue: Clinical Pharmacokinetics
Publisher: Springer Science and Business Media LLC
Published: 2006
Volume: 45
Issue: 5
Pages: 511-542
ISSN: 0312-5963 (ISSN-L)
DOI: 10.2165/00003088-200645050-00006
OpenAlex: W2146393360
Cited by: 352
References: 76
Citations by year: 2026: 10 · 2025: 13 · 2024: 10 · 2023: 13 · 2022: 18 · 2021: 17 · 2020: 16 · 2019: 17 · 2018: 13 · 2017: 14 · 2016: 20 · 2015: 19 · 2014: 19 · 2013: 19 · 2012: 26
FWCI: 20.15
Type: journal article
Language: en
Open access: closed
Locations: Clinical Pharmacokinetics (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
Keywords: physiologically based pharmacokinetic modelling, human pharmacokinetic prediction, allometry, plasma concentration-time curve, oral clearance, volume of distribution, elimination half-life, prediction accuracy, pharmaceutical compounds
MeSH terms: Animals, Pharmaceutical Preparations, Humans, Models, Biological, Pharmacokinetics

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

A Novel Strategy for Physiologically Based Predictions of Human Pharmacokinetics

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks