Effect of methylprednisolone on CYP3A4-mediated drug metabolism in vivo

Objective: To study the effects of methylprednisolone on the pharmacokineti cs and pharmacodynamics of triazolam. Methods: In this three-phase cross-over study, ten healthy subjects receive d 0.25 mg oral triazolam on three occasions: on day I (no pretreatment, con trol), on day 8 (1 h after a single dose of 32 mg oral methylprednisolone) and on day 18 (after further treatment with 8 mg oral methylprednisolone da ily for 9 days). The plasma concentrations of triazolam were determined up to 10 h, and its effects were measured using four psychomotor tests up to 6 h. Results: The single dose of methylprednisolone showed no significant effect s on the pharmacokinetics of triazolam. However, the Digit Symbol Substitut ion Test result was better (P < 0.05) during the single-dose methylpredniso lone phase than during the control phase, the other three tests showing no differences between the phases, The multiple-dose treatment with methylpred nisolone reduced the mean peak plasma concentration (C-max) of triazolam by 30% (P < 0.05) but had no significant effects on the time to C-max (t(max) ), elimination half-life (t(1/2)), area under the plasma concentration-time curve from 0 h to 10 h (AUC(0-10) h) and AUC(0-infinity) and did not alter the effects of triazolam. Conclusion: A single, relatively high dose of methylprednisolone (32 mg) di d not affect cytochrome P-450 (CYP)3A4 activity, and treatment with 8 mg me thylprednisolone daily for 9 days did not result in clinically significant induction of CYP3A4.