CYP2C76-mediated species difference in drug metabolism: A comparison of pitavastatin metabolism between monkeys and humans

Abstract

The monkey is often used to predict metabolism of drugs in humans since it generally shows a metabolic pattern similar to humans. However, metabolic profiles different from humans are occasionally seen in monkeys for some drugs including pitavastatin. Recently, we have successfully identified a monkey-specific cytochrome P450 (CYP) 2C76, which possibly accounts for a species difference between monkeys and humans because of its sequence and functional uniqueness. The present study on the role of CYP2C76 and other monkey CYP2Cs in pitavastatin metabolism, as an example, has revealed that CYP2C76 is important for the metabolism of the lactone form, indicating a major role of CYP2C76 for the difference in the metabolism of pitavastatin and possibly other drugs between monkeys and humans. The current investigation on the involvement of CYP2C76 in the metabolism of other drugs is expected to reveal further the further importance of this monkey-specific drug-metabolizing enzyme.

Key Words::

• CYP2C76
• monkey-specific
• species difference
• drug metabolism
• pitavastatin

Acknowledgements

The authors are grateful to Mr Junji Kojima, Mr Tsuyoshi Saito and Mr Shin-ichiro Ogawa for their technical assistant and invaluable suggestions.