Comparison of Maximum Drug Concentration and Area Under the Time‐Concentration Curve Between Humans and Animals for Oral and Intravenous Investigational Drugs

The study compared maximum drug concentration (C(max)) and area under the time-concentration curve (AUC) after normalization of doses to body weight and to body surface area and developed relationships for C(max) and AUC between humans and animals for 75 oral and 10 intravenous investigational drugs. For the oral drugs, animal-human ratios of C(max) were different among animals in both normalizations. Surface area-normalized AUC ratios were not different, whereas weight-normalized ones were different. For both normalizations for intravenous drugs, AUC ratios were not different. Drugs exhibiting 1/10 or smaller ratios tended to have low bioavailability. Regression of the relationships for dose-normalized C(max) and AUC transformed logarithmically between humans and animals were significant for the drugs with relatively high bioavailability. As approaches for predicting human C(max) and AUC from animals, surface area normalization seems to surpass weight normalization, and the equation obtained can be applied to drugs with high bioavailability.