Steroid-specific and anticonvulsant interaction aspects of troleandomycin-steroid therapy

Troleandomycin (TAO) is a macrolide antibiotic that has an apparent "steroid-sparing" effect when used in the treatment of severe steroid-dependent asthmatic patients. Recent observations demonstrated the effect of TAO on inhibiting methylprednisolone elimination, possibly contributing to its beneficial effects. Prednisolone and methylprednisolone disposition were studied before and 1 wk after initiation of TAO therapy in three patients. Methylprednisolone elimination was characteristically impaired in the presence of TAO therapy; however, there was no apparent effect on prednisolone elimination. Methylprednisolone elimination was also evaluated before and after initiation of TAO therapy in three patients receiving concomitant anticonvulsant therapy with phenobarbital-1, phenytoin-2. Methylprednisolone clearance before TAO was at least 4 times faster than normal and was probably related to enzyme induction by the anticonvulsant medication. Methylprednisolone clearance was subsequently reduced by approximately 70% in the presence of TAO therapy. The effect of TAO on corticosteroid disposition is steroid-specific and TAO can diminish the effect of certain drugs on the induction of corticosteroid metabolism.