RT Journal Article
SR Electronic
T1 Exploration of the African Green Monkey as a Preclinical Pharmacokinetic Model: Intravenous Pharmacokinetic Parameters
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 715
OP 720
DO 10.1124/dmd.107.019315
VO 36
IS 4
A1 Keith W. Ward
A1 David James Coon
A1 Daniel Magiera
A1 Sanjeev Bhadresa
A1 Ernell Nisbett
A1 Matthew S. Lawrence
YR 2008
UL http://dmd.aspetjournals.org/content/36/4/715.abstract
AB The value of cynomolgus and rhesus monkeys to predict human pharmacokinetic parameters has been well established in recent years. However, practical limitations on cost and accessibility can often be a deterrent to obtain data in these valuable species, and the characterization of the predictive power of other nonhuman primates would be useful. Therefore, the present investigation was designed to evaluate the pharmacokinetics of a test set of marketed compounds in the African green monkey, to compare the pharmacokinetics of these agents between nonhuman primate species, and to validate the ability of the African green monkey to predict human pharmacokinetics. Intravenous pharmacokinetics were evaluated for 11 test compounds in this study and compared with data from rats, dogs, cynomolgus/rhesus monkeys, and humans. The results from this investigation indicate that African green monkeys deliver reasonable prediction of human clearance and mean residence time and volume of distribution, although somewhat less accurately than cynomolgus and rhesus monkeys, particularly for volume of distribution, potentially because of body size or composition or experimental design differences. Furthermore, use of an optimized clearance prediction algorithm from the literature enhanced predictivity over a simple liver blood flow-based extrapolation methodology. The data from this study show that African green monkeys have the potential to be used as a surrogate for cynomolgus or rhesus monkeys in preclinical pharmacokinetic studies, particularly for the study of clearance processes, and should be considered as an alternate nonhuman primate test species.