The effect of troleandomycin on methylprednisolone elimination.

Troleandomoycin (TAO), a macrolide antibiotic, has an apparent "steroid-sparing" effect when used in the treatment of severe steroid-dependent asthma. This study was designed to investigate the effect of TAO on methylprednisolone elimination. Pharmacokinetic studies were performed before and 1 wk after starting TAO in 10 severe steroid-dependent asthmatics. Baseline total body clearance of methylprednisolone was 406 +/- 139 (mean +/- SD) ml/min/1.73 m2 and decreased significantly (p < 0.001) to 146 +/- 57 ml/min/1.73 m2 1 wk after TAO therapy was initiated. Methylprednisolone half-life was 2.46 +/- 0.75 hr before TAO and increased significantly (p < 0.01) to 4.63 +/- 1.35 hr after 1 wk on TAO therapy. A follow-up evaluation of methylprednisolone pharmacokinetics in three patients after at least 1 mo on TAO therapy demonstrated continuation of the reduced methylprednisolone elimination. TAO inhibition of methylprednisolone clearance may contribute to the beneficial effects observed initially with combined methylprednisolone-troleandomycin therapy in severe steroid-dependent asthma.