THE EFFECTS OF MENOPAUSE AND HORMONE REPLACEMENT THERAPIES ON PREDNISOLONE AND ERYTHROMYCIN PHARMACOKINETICS

The pharmacokinetics of oral and intravenous prednisolone and intraven ous erythromycin were examined in premenopausal women, postmenopausal women not undergoing hormone replacement therapy, post-menopausal wome n undergoing estrogen replacement therapy, and postmenopausal women un dergoing estrogen and progestin replacement therapy, The unbound clear ance of prednisolone was significantly lower in postmenopausal women ( 11.6 +/- 2.3 ml/min/kg) than in premenopausal women (16.6 +/- 3.5 ml/m in/kg). A comparable difference was also observed in total clearance a nd in half-life. The bioavailability and volume of distribution of pre dnisolone were unaffected by menopausal status, Hormone replacement th erapies did not significantly affect prednisolone pharmacokinetics. In contrast to prednisolone elimination, erythromycin elimination, as me asured by the erythromycin breath test, was not significantly affected by either menopausal status or hormone replacement therapy, In additi on, there was no correlation between prednisolone clearance and the er ythromycin breath test result, Although cytochrome P450 3A4 (CYP3A4) h as been implicated in steroid hormone metabolism, these results sugges t that another enzyme system, which is decreased in menopause (rather than simply an age effect), is also involved in prednisolone metabolis m.