Effect of methylprednisolone on CYP3A4-mediated drug metabolism in vivo

Abstract.

Objective: To study the effects of methylprednisolone on the pharmacokinetics and pharmacodynamics of triazolam. Methods: In this three-phase cross-over study, ten healthy subjects received 0.25 mg oral triazolam on three occasions: on day 1 (no pretreatment, control), 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 daily 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 effects on the pharmacokinetics of triazolam. However, the Digit Symbol Substitution Test result was better (P<0.05) during the single-dose methylprednisolone phase than during the control phase, the other three tests showing no differences between the phases. The multiple-dose treatment with methylprednisolone 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–∞ and did not alter the effects of triazolam. Conclusion: A single, relatively high dose of methylprednisolone (32 mg) did not affect cytochrome P₄₅₀ (CYP)3A4 activity, and treatment with 8 mg methylprednisolone daily for 9 days did not result in clinically significant induction of CYP3A4.