ORAL-CONTRACEPTIVE EFFECTS ON METHYLPREDNISOLONE PHARMACOKINETICS ANDPHARMACODYNAMICS

Objective: Oral contraceptive (OC) steroids alter the disposition of n umerous drugs, including corticosteroids, We investigated the pharmaco kinetics and pharmacodynamics of methylprednisolone. Methods: Twelve w omen (six women used OC steroids and six women did not) received intra venous methylprednisolone (0.6 mg/kg ideal body weight), Methylprednis olone disposition was assessed from plasma concentrations, Pharmacodyn amic parameters measured were plasma cortisol, whole blood histamine ( reflecting basophils), and blood helper T lymphocytes. Results: Methyl prednisolone clearance was significantly decreased in the women who us ed OC steroids (0.298 versus 0.447 L/hr/kg), resulting in a longer eli mination half-life (2.20 versus 1.72 hours), With use of indirect resp onse models, significant differences were observed with the cortisol a nd basophil responses, A larger value for the concentration that inhib its the zero-order production rate by 50% (0.37 versus 0.11 ng/ml) was observed in the women who used OC steroids for suppression of cortiso l secretion, indicating less sensitivity to the suppressive effects of methylprednisolone. Greater net suppression of basophils was observed in the users of OC steroids (area under the response curve, 694 versu s 401 ng hr/ml). No differences were observed for helper T-cell respon ses. Conclusion: OC steroids appear to inhibit methylprednisolone meta bolism, However, mixed changes in several responses occur, indicating that women can probably receive similar doses of methylprednisolone ir respective of OC steroid use.