| Autor: |
Slayter, Kathryn L., Ludwig, Elizabeth A., Lew, Kim H., Middleton, Elliott, Ferry, James J., Jusko, William J. |
| Zdroj: |
Clinical Pharmacology & Therapeutics; March 1996, Vol. 59 Issue: 3 p312-321, 10p |
| Abstrakt: |
Objective: Oral contraceptive (OC) steroids alter the disposition of numerous drugs, including corticosteroids. We investigated the pharmacokinetics and pharmacodynamics of methylprednisolone.Methods: Twelve women (six women used OC steroids and six women did not) received intravenous methylprednisolone (0.6 mg/kg ideal body weight). Methylprednisolone disposition was assessed from plasma concentrations. Pharmacodynamic parameters measured were plasma cortisol, whole blood histamine (reflecting basophils), and blood helper T lymphocytes.Results: Methylprednisolone clearance was significantly decreased in the women who used OC steroids (0.298 versus 0.447 L/hr/kg), resulting in a longer elimination half-life (2.20 versus 1.72 hours). With use of indirect response models, significant differences were observed with the cortisol and basophil responses. A larger value for the concentration that inhibits 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 cortisol 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 versus 401 ng · hr/ml). No differences were observed for helper T-cell responses.Conclusion: OC steroids appear to inhibit methylprednisolone metabolism. However, mixed changes in several responses occur, indicating that women can probably receive similar doses of methylprednisolone irrespective of OC steroid use. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
Plný text