Tissue lipids and drug distribution: Dog versus rat
Abstract
A key parameter in whole-body physiologically based pharmacokinetic models is the tissue-to-plasma water partition coefficient (K(pu)), which is commonly assumed consistent across all species for all tissues for passively distributing drugs. Many drugs primarily bind to tissue lipids and although considerable tissue lipid concentration data exist in rodents, data on these and K(pu) values in larger animals and humans are sparse to negligible. To test the above assumption, lipid levels were quantified in 13 dog tissues, then compared with the values in rat, and used to predict and compare K(pu) values between these species. For many tissues, including muscle, lipid concentrations were comparable in dog and rat. However, spleen acidic phospholipid levels were sevenfold lower, skin neutral phospholipid threefold lower, and neutral lipids fivefold, 12-fold, and eightfold lower in brain, lung, and spleen, respectively, and fourfold higher in bone in dog than in rat. Such differences resulted in significant predicted K(pu) differences. In contrast, unbound volume of distribution (Vu(ss)), a global measure of distribution, showed generally good agreement (predictions and observations) between dog and rat for a diverse compound set, indicating tissues with large-predicted K(pu) species differences tend either to contribute to Vu(ss) to a limited extent, and/or occur in opposing directions tending to cancel each other out.
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Tissue-specific acidic phospholipid concentration data are only available for rats, dogs and humans.
“Tissue-specific acidic phospholipid concentration data are only available for rats, dogs and humans [51, 78]”
Cites
A SIMPLE METHOD FOR THE ISOLATION AND PURIFICATION OF TOTAL LIPIDES FROM ANIMAL TISSUES
Folch, J., Lees, M., & Stanley, G. H. S. (1957) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)64849-5 · Cited by 65,189 · see citing works
Physiological Parameters in Laboratory Animals and Humans
Davies, B., & Morris, T. (1993) · Pharmaceutical Research · doi:10.1023/a:1018943613122 · Cited by 2,930 · see citing works
Rodgers, T., & Rowland, M. (2006) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.20502 · Cited by 949 · see citing works
Self-citationRodgers, T., Leahy, D., & Rowland, M. (2005) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.20322 · Cited by 776 · see citing works
Self-citationMechanistic 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
Self-citationA Novel Strategy for Physiologically Based Predictions of Human Pharmacokinetics
Jones, H. M., Parrott, N., Jorga, K., & Lav??, T. (2006) · Clinical Pharmacokinetics · doi:10.2165/00003088-200645050-00006 · Cited by 352 · see citing works
Self-citationGeneral approach for the calculation of tissue to plasma partition coefficients
Schmitt, W. (2008) · Toxicology in Vitro · doi:10.1016/j.tiv.2007.09.010 · Cited by 349 · see citing works
Lipid composition of erythrocytes in various mammalian species
Nelson, G. J. (1967) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(67)90152-x · Cited by 314 · see citing works
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-citationBischoff, K. B., & Dedrick, R. L. (1968) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.2600570814 · Cited by 211 · see citing works
Evans, G. H., Nies, A. S., & Shand, D. G. (1973) · PubMed · Cited by 206 · see citing works
Species variations in phospholipid class distribution of organs: I. Kidney, liver and spleen
Rouser, G., Simon, G., & Kritchevsky, G. (1969) · Lipids · doi:10.1007/bf02531047 · Cited by 195 · see citing works
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-citationThe effect of storage on the fatty acid composition of human serum
Moilanen, T. P. S., & Nikkari, T. (1981) · Clinica Chimica Acta · doi:10.1016/0009-8981(81)90235-7 · Cited by 154 · see citing works
Species variations in phospholipid class distribution of organs: II. Heart and skeletal muscle
Simon, G., & Rouser, G. (1969) · Lipids · doi:10.1007/bf02531048 · Cited by 148 · see citing works
Siefert, H. M., Domdey-Bette, A., Henninger, K., et al. (1999) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/43.suppl_2.69 · Cited by 145 · see citing works
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-citationPeyret, T., Poulin, P., & Krishnan, K. (2010) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2010.09.010 · Cited by 136 · see citing works
Physiologically based pharmacokinetic study on a cyclosporin derivative, SDZ IMM 125
Kawai, R., Lemaire, M., Steimer, J., Bruelisauer, A., Niederberger, W., & Rowland, M. (1994) · Journal of pharmacokinetics and biopharmaceutics · doi:10.1007/bf02353860 · Cited by 133 · see citing works
Self-citationRodgers, T., Leahy, D. E., & Rowland, M. (2005) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.20323 · Cited by 131 · see citing works
Self-citationGlycolipids and other lipid constituents of normal human liver
Kwiterovich, P. O., Sloan, H. R., & Fredrickson, D. S. (1970) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)42968-2 · Cited by 131 · see citing works
Composition of neutral lipids from erythrocytes of common mammals
Nelson, G. J. (1967) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)39569-9 · Cited by 119 · see citing works
Lipid composition of testes from various species
Bieri, J. G., & Prival, E. L. (1965) · Comparative Biochemistry and Physiology · doi:10.1016/0010-406x(65)90131-3 · Cited by 105 · see citing works
Slatter, J. G., Adams, L. A., Bush, E. C., et al. (2002) · Xenobiotica · doi:10.1080/00498250210158249 · Cited by 101 · see citing works
Evans, G. H., Nies, A. S., & Shand, D. G. (1973) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)29572-6 · Cited by 92 · see citing works
Olar, T. T., AMANN, R. P., & Pickett, B. W. (1983) · Biology of Reproduction · doi:10.1095/biolreprod29.5.1114 · Cited by 90 · see citing works
Izumi, T., Enomoto, S., Hoshiyama, K., Sasahara, K., Shibukawa, A., Nakagawa, T., & Sugiyama, Y. (1996) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)13117-0 · 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
Variations among vertebrates of lung phospholipid class composition
Baxter, C. F., Rouser, G., & Simon, G. (1969) · Lipids · doi:10.1007/bf02532640 · Cited by 72 · see citing works
Species Differences in Distribution and Prediction of Human Vss from Preclinical Data
Berry, L. M., Li, C., & Zhao, Z. (2011) · Drug Metabolism and Disposition · doi:10.1124/dmd.111.040766 · Cited by 69 · see citing works
Harrison, L. I., & Gibaldi, M. (1977) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.2600661206 · Cited by 67 · see citing works
Poulin, P., & Haddad, S. (2012) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.23090 · Cited by 66 · see citing works
Renal Extraction of Gentamicin in Anesthetized Dogs
Chiu, P. J. S., Brown, A. D., Miller, G. H., et al. (1976) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.10.2.277 · Cited by 63 · see citing works
PHYSIOLOGICALLY BASED PHARMACOKINETICS OF BISPHENOL A
Shin, B. S., Kim, C., Jun, Y. S., et al. (2004) · Journal of Toxicology and Environmental Health · doi:10.1080/15287390490514615 · Cited by 60 · see citing works
Graham, H., Walker, M., Jones, O., Yates, J. W. T., Galetin, A., & Aarons, L. J. (2011) · Journal of Pharmacy and Pharmacology · doi:10.1111/j.2042-7158.2011.01429.x · Cited by 57 · see citing works
Pharmacokinetics of drugs in blood I. Unusual distribution of gentamicin
Lee, M. G., Chen, M., Huang, S., et al. (1981) · Biopharmaceutics & Drug Disposition · doi:10.1002/bdd.2510020110 · Cited by 37 · see citing works
Hayakawa, H., Fukushima, Y., Kato, H., Fukumoto, H., Kadota, T., Yamamoto, H., Kuroiwa, H., Nishigaki, J., & Tsuji, A. (2003) · Drug Metabolism and Disposition · doi:10.1124/dmd.31.11.1409 · Cited by 37 · see citing works
EFFECT OF I.V. ANAESTHESIA WITH PROPOFOL ON DRUG DISTRIBUTION AND METABOLISM IN THE DOG
Perry, S. M., Whelan, E., Shay, S. D., et al. (1991) · British Journal of Anaesthesia · doi:10.1093/bja/66.1.66 · Cited by 35 · see citing works
Pharmacokinetic Model for Simultaneous Determination of Drug Levels in Organs and Tissues
Chen, C. N., & Andrade, J. D. (1976) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.2600650522 · Cited by 33 · see citing works
Robbie, G., & Chiou, W. L. (1998) · Pharmaceutical Research · doi:10.1023/a:1011923704731 · Cited by 29 · see citing works
von Kleist, M., & Huisinga, W. (2007) · Journal of Pharmacokinetics and Pharmacodynamics · doi:10.1007/s10928-007-9071-3 · Cited by 29 · see citing works
Cárceles, C. M., Villamayor, L., Escudero, E., et al. (2005) · The Veterinary Journal · doi:10.1016/j.tvjl.2005.11.003 · Cited by 24 · see citing works
Plasma and erythrocyte Na, K, Cl and water in hypothermic and hyperthermic dogs
Spurr, G. B., & Barlow, G. (1959) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1959.197.3.648 · Cited by 11 · see citing works
Whittem, T., Parton, K. H., & Turner, K. (1996) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.40.5.1237 · Cited by 10 · see citing works
Zakaryan, A., Karageuzyan, K. G., Hovsepyan, L., et al. (2001) · International Immunology · doi:10.1093/intimm/13.9.1141 · Cited by 6 · see citing works
Pharmacokinetic interaction between diltiazem and amiodarone in the dog
David, J. B., & Bialer, M. (1989) · Biopharmaceutics & Drug Disposition · doi:10.1002/bdd.2510100409 · Cited by 5 · see citing works
The Effects of Trifluoperazine on Calcifying Tissues in the Immature Rat
Boskey, A. L., Lewinson, D., & Bullough, P. G. (1984) · Experimental Biology and Medicine · doi:10.3181/00379727-176-41856 · Cited by 4 · see citing works
Ramaswamy, M., & Wasan, K. M. (2001) · Drug Development and Industrial Pharmacy · doi:10.1081/ddc-100107252 · Cited by 2 · see citing works
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- Authors
- Rodgers, T., Jones, H. M., & Rowland, M.
- Affiliations
- University of Manchester (GB)
- Pfizer (United States) (US)
- Corresponding author
- Rodgers, Trudy
- ORCID
- Jones, Hannah M.
- Venue
- Journal of Pharmaceutical Sciences
- Publisher
- Elsevier BV
- Published
- 2012-12
- Volume
- 101
- Issue
- 12
- Pages
- 4615-4626
- ISSN
- 0022-3549 (ISSN-L)
- OpenAlex
- W2029267669
- Cited by
- 31
- References
- 48
- Citations by year
- 2026: 1 · 2024: 3 · 2023: 1 · 2022: 1 · 2020: 2 · 2019: 4 · 2018: 4 · 2017: 2 · 2016: 1 · 2015: 4 · 2014: 1 · 2013: 6 · 2012: 1
- FWCI
- 4.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmaceutical Sciences (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Manchester
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Keywords
- tissue lipids, drug distribution, tissue-to-plasma partition coefficient, species differences, dogs, rats, physiologically based pharmacokinetic modeling, phospholipids
- MeSH terms
- Animals, Computer Simulation, Dogs, Lipids, Male, Models, Biological, Pharmacokinetics, Tissue Distribution, Rats, Sprague-Dawley, Rats
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