Journal of Drug Metabolism & Toxicology
Open Access
ISSN: 2157-7609
ISSN: 2157-7609
Iwano S
Japan
Research Article
Species Differences in the Pharmacokinetic Parameters of Cytochrome P450 Probe Substrates between Experimental Animals, such as Mice, Rats, Dogs, Monkeys, and Microminipigs, and Humans
Author(s): Sakai C, Iwano S, Yamazaki Y, Ando A, Nakane F, Kouno M, Yamazaki H and Miyamoto YSakai C, Iwano S, Yamazaki Y, Ando A, Nakane F, Kouno M, Yamazaki H and Miyamoto Y
To clarify species differences in the pharmacokinetic parameters of cytochrome P450 (CYP) activities between humans and experimental animals, we assessed several CYP activities in mice, rats, dogs, monkeys, and microminipigs, using the simultaneous administration of typical human CYP substrates, such as caffeine (human CYP1A2 substrate), losartan (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), and midazolam (CYP3A), to these animals. The intrinsic clearance (CLint) of these 5 substrates was also examined using the liver microsomes of humans and the experimental animals. The high bioavailabilities (BAs) and low CLint values of caffeine in the experimental animals were similar to those in humans. Mice and monkeys had lower BAs and higher CLint values of losartan than those in humans. Mice, rats, and monkeys had lower BAs and higher CLint values of omeprazole than those in hum.. View More»