Comparison of Oral Absorption and Bioavailability of Drugs Between Monkey and Human

Purpose. To compare the oral absorption and bioavailability of numerous drugs with a wide variety of physicochemical and pharmacological properties between humans and monkeys and to explore potential reasons for the findings. Methods. Data for fraction of dose absorbed (F _a) and oral absolute bioavailability (F) were obtained by an extensive Medline database search. Inclusion and exclusion criteria were the same as those reported in our previous studies. A total of 43 and 35 drugs were selected for F _a and F comparison, respectively. The time to reach peak concentration (t _max), total clearance, and nonrenal clearance were evaluated for 15, 28, and 13 drugs, respectively. Results. F _a values in monkeys were similar or identical to those in humans. Additionally, similar t _max values were seen in monkeys and humans at comparable doses, thus indicating comparable absorption kinetics between the two species. Conversely, F values in monkeys were generally lower with coumarin being a marked exception. Both total and nonrenal clearances were evaluated and found to be generally greater in monkeys, supporting a generally higher first-pass metabolism and lower F in this species. This was also supported by published data suggesting greater in vitro hepatic drug metabolism for monkeys as compared to humans. Conclusions. Monkeys appear to be a good predictor of F _a in humans. However, a generally lower F makes monkeys a potentially poor predictor of human F. Higher reported metabolic clearances and hepatic enzyme activities in monkeys may account for this observation.