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  • Title: Effect of methylprednisolone on CYP3A4-mediated drug metabolism in vivo.
    Author: Villikka K, Varis T, Backman JT, Neuvonen PJ, Kivistö KT.
    Journal: Eur J Clin Pharmacol; 2001 Sep; 57(6-7):457-60. PubMed ID: 11699609.
    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 (Cmax) of triazolam by 30% (P < 0.05) but had no significant effects on the time to Cmax (tmax), 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) 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.
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