A NOVEL MODEL FOR PREDICTION OF HUMAN DRUG CLEARANCE BY ALLOMETRIC SCALING
Abstract
Sixty-one sets of clearance (CL) values in animal species were allometrically scaled for predicting human clearance. Unbound fractions (f(u)) of drug in plasma in rats and humans were obtained from the literature. A model was developed to predict human CL: CL=33.35 ml/min x (a/Rf(u))(0.770), where Rf(u) is the f(u) ratio between rats and humans and a is the coefficient obtained from allometric scaling. The new model was compared with simple allometric scaling and the "rule of exponents" (ROE). Results indicated that the new model provided better predictability for human values of CL than did ROE. It is especially significant that for the first time the proposed model improves the prediction of CL for drugs illustrating large vertical allometry.
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Interspecies scaling, allometry, physiological time, and the ground plan of pharmacokinetics
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- Authors
- Tang, H., & Mayersohn, M.
- Affiliations
- University of Arizona (US)
- ORCID
- Tang, Huadong
- Venue
- Drug Metabolism and Disposition
- Publisher
- Elsevier BV
- Published
- 2005-09
- Volume
- 33
- Issue
- 9
- Pages
- 1297-1303
- ISSN
- 0090-9556 (ISSN-L)
- OpenAlex
- W2138212930
- Cited by
- 141
- References
- 4
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 5 · 2023: 4 · 2022: 6 · 2021: 7 · 2020: 4 · 2019: 6 · 2018: 6 · 2017: 5 · 2016: 9 · 2015: 8 · 2014: 10 · 2013: 3 · 2012: 8
- FWCI
- 5.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Drug Metabolism and Disposition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Pfizer
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
- Keywords
- drug clearance prediction, allometric scaling, unbound fraction, plasma protein binding, interspecies scaling, rats
- MeSH terms
- Animals, Pharmaceutical Preparations, Humans, Metabolic Clearance Rate, Models, Biological, Pharmacokinetics, Species Specificity, Water, 1-Octanol, Rats
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