RT Journal Article SR Electronic T1 A COMPREHENSIVE QUANTITATIVE AND QUALITATIVE EVALUATION OF EXTRAPOLATION OF INTRAVENOUS PHARMACOKINETIC PARAMETERS FROM RAT, DOG, AND MONKEY TO HUMANS. II. VOLUME OF DISTRIBUTION AND MEAN RESIDENCE TIME JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 612 OP 619 DO 10.1124/dmd.32.6.612 VO 32 IS 6 A1 Keith W. Ward A1 Brian R. Smith YR 2004 UL http://dmd.aspetjournals.org/content/32/6/612.abstract AB Our laboratory is engaged in an ongoing analysis of a 103-compound data set containing reliable intravenous pharmacokinetic parameters in the rat, dog, monkey, and human, and we have previously reported our findings regarding extrapolation of clearance. In this article, we report on our findings regarding volume of distribution and mean residence time. Various allometric and nonallometric methods were used to predict human volume of distribution based on preclinical pharmacokinetic data; clearance and volume of distribution values generated by various means were then used to estimate mean residence time. From both a quantitative and qualitative perspective, estimating human volume and mean residence time based on monkey data alone was the most accurate approach evaluated. For volume, estimation based on monkey data alone was quantitatively the least biased of all approaches evaluated. Additionally, prediction of mean residence time based on clearance and volume from the monkey was the only extrapolation method that exhibited a positive, rather than negative, bias. None of the allometric scaling approaches investigated afforded optimal predictivity for either volume or mean residence time, and neither the correlation coefficient nor the allometric exponent allowed a prospective estimation of predictive success or failure. These observations regarding volume and mean residence time confirm our earlier results with clearance, and further confirm the value of the monkey as a species for pharmacokinetic lead optimization. The American Society for Pharmacology and Experimental Therapeutics