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Interspecies allometric meta‐analysis of the comparative pharmacokinetics of 85 drugs across veterinary and laboratory animal species
Author(s) -
Huang Q.,
Gehring R.,
Tell L. A.,
Li M.,
Riviere J. E.
Publication year - 2015
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/jvp.12174
Subject(s) - pharmacokinetics , volume of distribution , pharmacology , allometry , veterinary medicine , bioavailability , veterinary drug , medicine , biology , chemistry , chromatography , ecology
Allometric scaling is widely used for the determination of first dosage regimen and the interpolation or extrapolation of pharmacokinetic parameters across many animal species during drug development. In this article, 85 drugs used in veterinary medicine obtained from the F ood A nimal R esidue A voidance D atabank database were selected for allometric scaling analysis. Outlier species were identified by statistical methods. The results showed that 77% and 88% of drugs displayed significant correlations between total systemic clearance ( CL ) and volume of distribution at steady status (Vss) vs. body weight ( P < 0.05) on a log‐log scale, respectively. The distribution of the allometric exponent b for CL and Vss displays approximate normal distribution, with means (0.87 and 0.99) and standard deviations (0.143 and 0.157) for CL and Vss, respectively. Twelve drugs were identified to have at least one outlier species for CL and ten drugs for Vss. The human CL and Vss were predicted for selected drugs by the obtained allometric equations. The predicted CL and Vss were within a threefold error compared to observed values, except the predicted CL values for antipyrine, warfarin and diazepam. The results can be used to estimate cross‐species pharmacokinetic profiles for predicting drug dosages in veterinary species, and to identify those species for which interpolation or extrapolation of pharmacokinetics properties may be problematic.