Expression and induction of CYP2C P450 enzymes in primary cultures of human hepatocytes. Drug Metab

Although CYP2C8, CYP2C9, and CYP2C19 play an important role in drug biotransformation, factors influencing the expres-sion and activity of these CYP2C P450s in human liver remain largely undefined. We used primary cultures of human hepato-cytes from 15 subjects to assess the inducibility of CYP2C enzyme expression by prototypical inducer agents, including rifampicin, dexamethasone, and phenobarbital. After culture for 72 h in serum-free medium on collagen, Western blotting revealed that CYP2C9 was the only CYP2C enzyme ex-pressed at appreciable levels in untreated hepatocytes. Sub-sequent treatment with 25 M rifampicin for 48 h elicited marked increases in CYP2C8 (700 761%), CYP2C19 (854%), and CYP2C9 (209 176%) protein content versus a 550 170 % enhancement of CYP3A4 enzyme levels. Par