Cytochrome P4502C8: Substrates, inhibitors, pharmacogenetics, and clinical relevance

Cytochrome P450 (CYP) 2C9 has been a relatively neglected member of the human CYP2C family. Over the period from 2000 through 2003, PubMed searches with the key word CYP2C8 returned only 10% to 15% of the citations obtained for all of the CYP2C enzymes combined. However, in the past year a crystal structure for CYP2C8 has been described, new inhibitors and probe substrates for the enzyme have been in development, the first case study was published linking CYP2C8 genetic polymorphisms to a disease state, and there has been an increasing awareness of the role that CYP2C8 plays in the disposition of therapeutic agents, especially from the pharmacogenetic and drug-drug interaction perspectives. This report discusses baseline characteristics of the enzyme and summarizes recent developments in these areas and their clinical relevance.