Delayed De-Induction Of Cyp2c9 Compared To Cyp3a After Discontinuation Of Rifampicin: Report Of Two Cases

Objective: Timely dose reduction of concomitant medications is important after withdrawal of rifampicin, a CYP inducer. However, little is known about the differences in the time course of deinduction for various CYP isoforms. To clarify the time courses of deinduction of CYP2C9 and CYP3A activities after rifampicin withdrawal, we monitored these enzyme activities in 2 patients over time after discontinuing rifampicin. Materials and methods: Two patients (aged 70 and 80 years) received warfarin and rifampicin for anticoagulation and antituberculosis therapy, respectively. Warfarin doses were increased due to rifampicin-induced CYP activity. Upon completion of antituberculosis therapy, rifampicin was discontinued and warfarin doses were titrated downward according to prothrombin time. We monitored CYP2C9 and CYP3A activities over their clinical courses by measuring the metabolic clearance of S-warfarin to S-7-hydroxywarfarin and that of cortisol to 6 beta-hydroxycortisol, respectively. Results: In both patients, the time courses of CYP2C9 deinduction appeared to be delayed compared to CYP3A. Conclusion: Our findings suggest that a uniform dose reduction protocol for drugs metabolized by different CYP isoforms may be unsafe after rifampicin withdrawal.