Evaluation of using dog as an animal model to study the fraction of oral dose absorbed of 43 drugs in humans.

摘要

PURPOSE: To conduct a retrospective evaluation of using dog as an animal model to study the fraction of oral dose absorbed (F) of 43 drugs in humans and to briefly discuss potential factors that might have contributed to the observed differences in absorption. METHODS: Mean human and dog absorption data obtained under fasted state of 43 drugs with markedly different physicochemical and pharmacological properties and with mean F values ranging from 0.015 to 1.0 were obtained from the literature. Correlation of F values between humans and dogs was studied. Based on the same references, additional F data for humans and rats were also obtained for 18 drugs. RESULTS: Among the 43 drugs studied, 22 drugs were virtually completely absorbed in both dogs and humans. However, the overall correlation was relatively poor (r2 = 0.5123) as compared to the earlier rat vs. human study on 64 drugs (r2 = 0.975). Several drugs showed much better absorption in dogs than in humans. Marked differences in the nonliner absorption profiles between the two species were found for some drugs. Also, some drugs had much longer Tmax values and prolonged absorption in humans than in dogs that might be theoretically predicted. Data on 18 drugs further support great similarity in F between humans and rats reported earlier from our laboratory. CONCLUSIONS: Although dog has been commonly employed as an animal model for studying oral absorption in drug discovery and development, the present study suggests that one may need to exercise caution in the interpretation of data obtained. Exact reasons for the observed interspecies differences in oral absorption remain to be explored.