Interspecies scaling of biliary excreted drugs: prediction of human clearance and volume of distribution
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Iftekhar Mahmood
Abstract
Background: Interspecies differences in biliary excretion and the differences in bile flow rates make scaling across species difficult for drugs that are excreted in the bile. The objective of this study is to predict clearance (CL) and volume of distribution (V) for humans from animals for drugs that are excreted in the bile.
Methods: Clearance values of 10 drugs known to be excreted in the bile were selected from the literature. Scaling of CL was performed using at least three animal species. Using simple allometry and the rule of exponents (ROE), clearances of studied drugs were predicted in humans. Besides using the ROE, a ‘correction factor’ was applied adjusting bile flow rate based on the species body weight (bile flow mL/day/kg body weight) or liver weight (bile flow mL/day/kg liver weight). Using the ROE and combining it with the ‘correction factor’, the clearances of biliary excreted drugs were predicted for humans. V for 15 drugs (without any correction factor) that are excreted in the bile was also predicted for humans.
Results: The results of the study indicated that the ROE in association with the correction factors developed for the biliary excreted drugs substantially improved the prediction of human clearance for drugs that are excreted in the bile. In this study, there was no indication (unlike clearance) that the prediction of volume of drug distribution was affected (systematically under- or over-prediction) because of biliary excretion.
Conclusions: The clearance of drugs that are excreted in the bile can be predicted with reasonable accuracy using ROE and a correction factor.
©2012 by Walter de Gruyter Berlin Boston
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- Masthead
- Masthead
- Editorial
- Public Health Genomics and Personalized Healthcare: a pipeline from cell to society
- Review
- CYP2E1 potentiates toxicity in obesity and after chronic ethanol treatment
- Opinion paper
- Informatics competencies for healthcare professionals: the Technology Informatics Guiding Education Reform (TIGER) Initiative model
- Original articles
- Pharmacokinetics of tacrolimus in adult renal transplant recipients
- Interspecies scaling of biliary excreted drugs: prediction of human clearance and volume of distribution
- High-performance liquid chromatography method using ultraviolet detection for the quantification of aripiprazole and dehydroaripiprazole in psychiatric patients
- Case report
- Elevated liver enzymes resulting from an interaction between Raltegravir and Panax ginseng: a case report and brief review
- Miscellaneous
- European Best Practice Guidelines for Quality Assurance, Provision and Use of Genome-based Information and Technologies: the 2012 Declaration of Rome
- Congress Abstracts
- 6th Santorini Conference Biologie Prospective 2012
