Cited by 242Statistical Methods in Clinical TrialsPharmaceutical studies and practicesPharmacogenetics and Drug Metabolism

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Implementation of pharmacokinetic and pharmacodynamic strategies in early research phases of drug discovery and development at Novartis Institute of Biomedical Research

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Tuntland, Tove, Ethell, Brian, Kosaka, Takatoshi, Blasco, Francesca, Zang, Richard Xu, Jain, Monish, Gould, Ty, Hoffmaster, Keith·2014·Frontiers in Pharmacology

DOI 10.3389/fphar.2014.00174PMC PMC4112793

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Abstract

Characterizing the relationship between the pharmacokinetics (PK, concentration vs. time) and pharmacodynamics (PD, effect vs. time) is an important tool in the discovery and development of new drugs in the pharmaceutical industry. The purpose of this publication is to serve as a guide for drug discovery scientists toward optimal design and conduct of PK/PD studies in the research phase. This review is a result of the collaborative efforts of DMPK scientists from various Metabolism and Pharmacokinetic (MAP) departments of the global organization Novartis Institute of Biomedical Research (NIBR). We recommend that PK/PD strategies be implemented in early research phases of drug discovery projects to enable successful transition to drug development. Effective PK/PD study design, analysis, and interpretation can help scientists elucidate the relationship between PK and PD, understand the mechanism of drug action, and identify PK properties for further improvement and optimal compound design. Additionally, PK/PD modeling can help increase the translation of in vitro compound potency to the in vivo setting, reduce the number of in vivo animal studies, and improve translation of findings from preclinical species into the clinical setting. This review focuses on three important elements of successful PK/PD studies, namely partnership among key scientists involved in the study execution; parameters that influence study designs; and data analysis and interpretation. Specific examples and case studies are highlighted to help demonstrate key points for consideration. The intent is to provide a broad PK/PD foundation for colleagues in the pharmaceutical industry and serve as a tool to promote appropriate discussions on early research project teams with key scientists involved in PK/PD studies.

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Craig, W. A. (1998) · Clinical Infectious Diseases · doi:10.1086/516284 · Cited by 2,908
Monoclonal Antibody Pharmacokinetics and Pharmacodynamics
Wang, W., Wang, E., & Balthasar, J. (2008) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2008.170 · Cited by 978
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Smith, D. A., Di, L., & Kerns, E. H. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3287 · Cited by 925
Antibody Pharmacokinetics and Pharmacodynamics
Lobo, E. D., Hansen, R. J., & Balthasar, J. P. (2004) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.20178 · Cited by 909
Pharmacokinetic/pharmacodynamic data analysis : concepts and applications
Gabrielsson, J., & Weiner, D. (2002) · Cited by 704
Antimicrobial Resistance: Pharmacokinetics‐Pharmacodynamics of Antimicrobial Therapy: It’s Not Just for Mice Anymore
Ambrose, P. G., Bhavnani, S. M., Rubino, C. M., Louie, A., Gumbo, T., Forrest, A., & Drusano, G. L. (2007) · Clinical Infectious Diseases · doi:10.1086/510079 · Cited by 697
Kidney injury molecule-1 outperforms traditional biomarkers of kidney injury in preclinical biomarker qualification studies
Vaidya, V. S., Ozer, J. S., Dieterle, F., Collings, F. B., Ramírez, V., Troth, S. P., Muniappa, N., Thudium, D. T., Gerhold, D. L., Holder, D., et al. (2010) · Nature Biotechnology · doi:10.1038/nbt.1623 · Cited by 662
Predictive Pharmacokinetic-Pharmacodynamic Modeling of Tumor Growth Kinetics in Xenograft Models after Administration of Anticancer Agents
Simeoni, M., Magni, P., Cammia, C., Nicolao, G. D., Croci, V., Pesenti, E. A., Germani, M., Poggesi, I., & Rocchetti, M. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-2524 · Cited by 509
Elimination mechanisms of therapeutic monoclonal antibodies
Tabrizi, M. A., Tseng, C.-M. L., & Roskos, L. K. (2006) · Drug Discovery Today · doi:10.1016/s1359-6446(05)03638-x · Cited by 479
BRAFV600E: Implications for Carcinogenesis and Molecular Therapy
Dorris, E., O’Leary, J. J., & Sheils, O. M. (2011) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-10-0799 · Cited by 473

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McCully, C. L., Rodgers, L. T., Garica, R. C., Thomas, M. L., Peer, C. J., Figg, W. D., Barnard, D. E., & Warren, K. E. (2020) · Comparative Medicine · doi:10.30802/aalas-cm-99-990010 · Cited by 10
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Wang, M., Kuldharan, S., Shenoy, A., Reddy, S., Rex, K. L., Osgood, T., Wahlstrom, J. L., & Dahal, U. P. (2024) · Drug Metabolism and Disposition · doi:10.1124/dmd.124.001698 · Cited by 3
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Marques, S. M., & Kumar, L. (2022) · Springer eBooks · doi:10.1007/978-3-030-83395-4_15 · Cited by 3
Transition modeling of neuropsychiatric impairment in HIV
Bisaso, K. R., Mukonzo, J., & Ette, E. (2016) · Computers in Biology and Medicine · doi:10.1016/j.compbiomed.2016.04.011 · Cited by 3
In Vitro Nanotoxicity: Toward the Development of Safe and Effective Treatments
Bueno, J. (2020) · Nanotechnology in the life sciences · doi:10.1007/978-3-030-43855-5_4 · Cited by 4
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Klotsman, M., Coquery, S., Sathyan, G., Naageshwaran, V., Shivanand, P., Fairchild, A. J., Garden, O. A., & Anderson, W. H. (2021) · Frontiers in Veterinary Science · doi:10.3389/fvets.2020.611404 · Cited by 3
“, the PK/PD relationship) in a canine model is an important step (24, 25) that will help to establish dosing regimens and standardize treatment protocols for dogs presenting with immune-mediated diseases.”
Background
Advances in Biomarkers and Diagnostic Tools for Disabilities: Historical Development and Future Prospects
Thomas, S. M., & Veerabathiran, R. (2024) · Springer eBooks · doi:10.1007/978-3-031-40858-8_401-1 · Cited by 3
Population Modelling
Patil, D., Sahoo, J., Pai, R. V., & G., S. N. K. R. (2025) · Springer eBooks · doi:10.1007/978-981-96-4154-3_4 · Cited by 2
Fermented Bamboo Shoots as a Source of Natural HRAS Inhibitors: An Integrative Metabolomics, Pharmacokinetic, and Molecular Simulation Study for Cancer Therapy
Das, R., Thatal, B., & Tamang, B. (2026) · ChemistrySelect · doi:10.1002/slct.202504027 · Cited by 2
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Monogue, M. L., Sanders, J. M., Mercuro, N. J., Hodge, C. K., Golnabi, E. Y., Carettini, T., Yen, C. F., & Cutrell, J. B. (2026) · Open Forum Infectious Diseases · doi:10.1093/ofid/ofag093 · Cited by 2
“The significance of PK/PD data in preclinical studies and regulatory submissions has evolved over time, in concert with our understanding of this science [4, 5].”
T-World Virtual Human Cardiomyocyte. II. Organ-Scale Simulations and Applications
Tomek, J., Holmes, M., Martinez‐Navarro, H., Zhou, X., Hasaballa, A. I., Wang, Z. J., Berg, L. A., Bertrand, A., Colman, M. A., Bueno‐Orovio, A., et al. (2026) · Circulation Research · doi:10.1161/circresaha.125.328123 · Cited by 2
Modelling the role of the microbiome in antimicrobial resistance across scales
Pagani, L., León‐Sampedro, R., Amicone, M., Tepekule, B., Witzany, C., Brugger, S. D., de Vos, M. G. J., Mitri, S., Bakkeren, E., Bottery, M. J., et al. (2026) · Nature Microbiology · doi:10.1038/s41564-026-02390-8 · Cited by 3
“In vitro 164,166,170,171,174,175,178 and in vivo/in situ 168,169,176,177 experiments to clinical, community and environmental surveillance, and can be mapped onto five core modelling components: interspecies interactions, spatial structure, mutations and HGT, antibiotic efficacy, and microbiome…”
Animal Models in Toxicologic Research: Nonhuman Primate
Chilton, J. A., Laing, S. T., & Bradley, A. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-821044-4.00014-5 · Cited by 2
Lead Optimisation: What You Should Know!
Ward, S. E., & Davis, A. M. (2023) · Royal Society of Chemistry eBooks · doi:10.1039/9781788018982-00720 · Cited by 2
Can we do better with Mylotarg? Model-based assessment of opportunities to improve therapeutic index
Stoddard, M., Yuan, L., Cooper, J., Neumar, C., Hibner, B., Gardner, H., & Chakravarty, A. (2024) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2024.117034 · Cited by 2
Sonochemically Synthesised Nano‐Stone Structured Vanadium Tungstate for Electrochemical Monitoring of Antibiotic Drug Nitrofurantoin in Real Samples
Mohanty, J., Manikanta, P., Mounesh, Nikam, R. R., Hareesha, N., Sandeep, S., & Nagaraja, B. M. (2024) · ChemistrySelect · doi:10.1002/slct.202403627 · Cited by 2
Mathematical modeling of vancomycin release from Poly-L-Lactic Acid-Coated implants
Thamvasupong, P., & Viravaidya‐Pasuwat, K. (2024) · PLoS ONE · doi:10.1371/journal.pone.0311521 · Cited by 2
“Before a delivery system can be translated into clinical practice, extensive safety data from animal studies are needed [8]; however, this approach can be costly and time-consuming, leading to delays in the development of innovative delivery systems [9].”
Background
Microfabricated platforms to quantitatively investigate cellular behavior under the influence of chemical gradients
Elitaş, M., Sadeghi, S., Karamahmutoğlu, H., Gözüaçık, D., & Turhal, N. S. (2017) · Biomedical Physics & Engineering Express · doi:10.1088/2057-1976/aa7400 · Cited by 2
Toxicity and Teratogenic Potential of Piplartine from Piper tuberculatum Jacq. during Embryonic Development in Mice (Mus musculus)
Silva, G. R., Miranda, L. T. G., da Silva, S. A. D. C. A., de Andrade, L. R., de Souza, N. C., Sá, B. S., de Santana, E. R., Vasconcelos, A. G., Moreira, D. C., Pic‐Taylor, A., et al. (2024) · Drugs and Drug Candidates · doi:10.3390/ddc3020021 · Cited by 2
“Moreover, the study did not delve into the pharmacokinetics and pharmacodynamics of piplartine, factors essential for understanding its systemic behavior, optimizing dosing, and foreseeing drug–drug interactions [36,37].”
Background
Opportunities and Challenges in the Development of Antiparasitic Drugs
Bello‐Akinosho, M., Afolabi, K. O., Chandra, H., Mayashinta, D. K., Setia, Y. D., Mishra, A. P., & Pohl‐Albertyn, C. (2023) · doi:10.1002/9781119878063.ch11 · Cited by 2
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Li, J., Hu, P., Zhou, L., Nagahama, F., & Chen, R. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1154026 · Cited by 1
“The population pharmacokinetics (Pop PK) approach allows for combining blood concentration data from different clinical groups (Rajman, 2008; Tuntland et al, 2014).”
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Comparative pharmacokinetic and bioequivalence of nine oral ivermectin formulations in dogs
Kim, S., Sayem, S. A. J., Chae, H., Park, S.-W., Gui, L., Park, S., & Kang, J. (2025) · Journal of Veterinary Science · doi:10.4142/jvs.25170 · Cited by 1
“This variability aligns with that of previous reports on generic IVM formulations [30] and highlights the importance of considering formulation type and its effect on systemic exposure [31].”
Intracellular Pharmacokinetics of Antidiabetic Drugs: A Focused Narrative Review of Subcellular Distribution (2015–2025)
Bafail, D. A. (2026) · Diseases · doi:10.3390/diseases14020062 · Cited by 1
“It connects a drug’s concentration at its specific site of action within the cell to its ultimate pharmacological effect [5,6].”
Influential
Harnessing human colonoid-derived monolayers as an in vitro platform for investigating accumulation, toxicity, and pharmacodynamics of small molecules
Canhão, P. G. M., Smeuninx, A., Geerinckx, S., Evers, R., Snoeys, J., Augustijns, P., & Kourula, S. (2026) · Toxicology in Vitro · doi:10.1016/j.tiv.2026.106221 · Cited by 1
Advances in light-addressable potentiometric sensors for biomarkers and biosensing applications
Noureen, B., Ma, Y., Wang, M., Khalid, Z., Chen, W., Qu, Z., Du, L., & Wu, C. (2026) · Chinese Medical Journal BioMed · doi:10.65457/cmjbm-2026-0003 · Cited by 1
Withania-derived bioactive compounds in cancer treatment: phytochemical foundations and translational oncology
Narayanan, M. (2026) · Oriental Pharmacy and Experimental Medicine · doi:10.1007/s13596-026-00919-0 · Cited by 1
Computational methods (in silico) and stem cells as alternatives to animals in research
Tyagi, N., Kumar, S., Gangenahalli, G. U., & Verma, Y. K. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-821748-1.00003-8 · Cited by 1
IONPs-Based Treatment Methods
Savari, M.-N., & Jabali, A. (2023) · Nanomedicine and nanotoxicology · doi:10.1007/978-981-99-6507-6_7 · Cited by 1
Pharmacodynamic biomarker for Hepatocellular carcinoma C: Model-based evaluation for pharmacokinetic–pharmacodynamic responses of drug
Dogra, N., Mishra, S., Mani, R. J., Aeri, V., & Katare, D. P. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-821972-0.00007-1 · Cited by 1
Antitumor efficacy of CHMFL-KIT-110 solid dispersion in mouse xenograft models of human gastrointestinal stromal tumors
Wang, S., Wang, C., Wang, X., Wang, X., Huang, L., Kuai, J., Wei, W., Lu, X., & Yan, S. (2021) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-021-04332-z · Cited by 1
Interspecies comparison of plasma metabolism and sample stabilization for quantitative bioanalyses: Application to (R)-CE3F4 in preclinical development, including metabolite identification by high-resolution mass spectrometry
Toussaint, B., Hillaireau, H., Jaccoulet, E., Cailleau, C., Legrand, P., Ambroise, Y., & Fattal, E. (2021) · Journal of Chromatography B · doi:10.1016/j.jchromb.2021.122943 · Cited by 1
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Cong, D., Song, J., Liu, Y., Tan, Y., Xue, W., Liu, X., Qi, W., Lu, J., Yuan, X., Zhou, Y., et al. (2022) · Neurology and Therapy · doi:10.1007/s40120-021-00314-8 · Cited by 1
“Evaluation of PD and PK parameters helps to integrate quantitative information about the pharmacologic properties of a compound with its PK [30].”
Background
Population pharmacokinetic/pharmacodynamic analysis of AK111, an IL-17A monoclonal antibody, in subjects with moderate-to-severe plaque psoriasis
Li, Q., Qiao, J., Jin, H., Chen, B., He, Z., Wang, G., Ni, X., Wang, M. M., Xia, M., Li, B., et al. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.966176 · Cited by 1
“Population PK-pharmacodynamic (PD) modeling, which links the concentration time course (including variation across dosing intervals) to the time course of the pharmacodynamic response, provides quantitative information to predict the drug exposure–response relationship (Tuntland et al., 2014; Overgaard et al., 2015).”
Background
Safety pharmacology during the COVID pandemic
Pugsley, M. K., Koshman, Y. E., de Korte, T., Authier, S., & Curtis, M. J. (2021) · Journal of Pharmacological and Toxicological Methods · doi:10.1016/j.vascn.2021.107089 · Cited by 1
Prediction of Drug Distribution to Each Tissue Using Random Forest Twice with In Vitro Experimental Values and Predicted Kp Values of Other TissuesPreprint
D, K. H. M., Yoshimura, S., Kageyama, M., & Iijima, T. (2023) · ChemRxiv · doi:10.26434/chemrxiv-2023-qsrxp · Cited by 1
Prédiction des constantes cinétiques de complexes protéine-ligand
Ziada, S. (2019) · doi:10.70675/1d581f29z4cb3z4657z941ezb57faa759067 · Cited by 1
Estudo do potencial terapêutico de fármacos e compostos sintéticos, livres ou incluídos em nanolipossomos: uma abordagem in vitro e experimental na leishmaniose visceral
Pinto, É. G. (2016) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.99.2016.tde-19042016-150040
Estimation of Kinetic Parameters From List-Mode Data Using an Indirect Approach
Ortiz, J. C. (2016) · UA Campus Repository (The University of Arizona)

Authors: Tuntland, T., Ethell, B., Kosaka, T., Blasco, F., Zang, R. X., Jain, M., Gould, T., & Hoffmaster, K.
Affiliations: Genomics Institute of the Novartis Research Foundation (US)
Novartis (Singapore) (SG)
Corresponding author: Tuntland, Tove
ORCID: Tuntland, Tove
Zang, Richard Xu
Venue: Frontiers in Pharmacology
Publisher: Frontiers Media SA
Published: 2014-07-28
Volume: 5
Pages: 174-174
ISSN: 1663-9812 (ISSN-L)
DOI: 10.3389/fphar.2014.00174
PMC: PMC4112793
OpenAlex: W2070719925
Cited by: 239
References: 70
Citations by year: 2026: 23 · 2025: 25 · 2024: 26 · 2023: 25 · 2022: 24 · 2021: 25 · 2020: 28 · 2019: 16 · 2018: 11 · 2017: 17 · 2016: 10 · 2015: 8
FWCI: 1.48
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
Locations: Frontiers in Pharmacology (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics: Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Keywords: pharmacokinetics, pharmacodynamics, pharmacokinetic-pharmacodynamic modeling, drug discovery, research design, data analysis and interpretation, mechanism of drug action, in vitro to in vivo translation, preclinical to clinical translation, compound design, inter-agency cooperation

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Implementation of pharmacokinetic and pharmacodynamic strategies in early research phases of drug discovery and development at Novartis Institute of Biomedical Research

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