Background: Methylprednisolone is a widely used glucocorticoid. In this study, a possible interaction of itraconazole, a potent inhibitor of CYP3A4, with orally administered methylprednisolone was examined.
Methods: In this double-blind, randomized, 2-phase crossover study, 10 healthy volunteers received either 200 mg itraconazole or placebo orally once a day for 4 days. On day 4, each subject ingested a dose of 16 mg methylprednisolone. Plasma concentrations of methylprednisolone, cortisol, itraconazole, and hydroxyitraconazole were determined by HPLC up to 24 hours.
Results: Itraconazole increased the total area under the plasma methylprednisolone concentration-time curve 3.9-fold compared with placebo (1968 +/- 470 ng.hr/mL versus 520 +/- 125 ng.hr/mL [mean +/- SD]; P < .001). The peak plasma concentration of methylprednisolone was increased 1.9-fold (221 +/- 49 ng/mL versus 118 +/- 25 ng/mL; P < .001), and its elimination half-life was increased 2.4-fold (4.4 +/- 0.7 hours versus 1.9 +/- 0.3 hours; P < .001) by itraconazole. The mean plasma cortisol concentration during the itraconazole phase, measured 24 hours after ingestion of methylprednisolone, was only about 13% of that during the placebo phase (18 +/- 23 ng/mL versus 139 +/- 60 ng/mL; P < .001).
Conclusions: Itraconazole considerably increases plasma concentrations and effects of oral methylprednisolone, probably by inhibiting its CYP3A4-mediated metabolism. Care should be taken if itraconazole or other potent inhibitors of CYP3A4 are used concomitantly with oral methylprednisolone, particularly during long-term use.