Correlation of Unbound Plasma Clearances of Fifteen Extensively Metabolized Drugs Between Humans and Rats

Unbound plasma clearances (CLu) in humans and rats of 15 extensively metabolized drugs (phe-nytoin, hexobarbital, pentobarbital, phenylbutazone, warfarin, tolbutamide, valproate, phenobarbital, amobarbital, quinidine, chlorpromazine, propranolol, pentazocin, antipyrine, and diazepam), studied earlier by Sawada et al. (J. Pharmacokin. Biopharm. 13:477–491, 1985), were calculated. It was found that the ratio of CLu per square meter of body surface area between human and rat ranged from 0.38 for pentobarbital to 2.34 for tolbutamide, with a mean ratio of 1.07. When body weight (BW) was used for correlation, the mean CLu was proportional to BW ^{0.657±0.0935}. A rationale for the above empirical findings is postulated. The present study seems to indicate the existence of a general similarity or predictability in the CLu of drugs between rats and humans. Low correlations were generally obtained when total (bound and unbound) plasma clearances were used for comparison.