Oral contraceptive effects on methylprednisolone pharmacokinetics and pharmacodynamics

Clin Pharmacol Ther. 1996 Mar;59(3):312-21. doi: 10.1016/S0009-9236(96)80009-9.


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 x 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.

PIP: At the Buffalo General Hospital in New York, researchers randomly assigned 6 healthy, nonobese women, 30-36 years old and using a triphasic oral contraceptive (OC) (Triphasil 28, Wyeth-Ayerst Laboratories), to either the baseline phase group or the group receiving an intravenous bolus of methylprednisolone sodium succinate at a dose of 0.6 mg/kg ideal body weight during the 2-week period after ovulation (i.e., luteal phase). These women were compared with 6 other women who did not use OCs but did receive the same dose of methylprednisolone. The purpose was to determine whether the adrenosuppressive, anti-inflammatory, and immunosuppressive effects of methylprednisolone differ in OC users. OC users experienced slower clearance of methylprednisolone (33% slower) than controls. This slower clearance rate contributed to a longer elimination half-life for methylprednisolone (2.2 vs. 1.72 hours; p 0.05). OC users also had a rate of slower elimination of cortisol than controls (0.180 vs. 0.276 hr-1; p 0.05). They had higher mean cortisol levels than controls (136 vs. 65 ng/ml). Women who used OCs for suppression of cortisol secretion had a larger value for the concentration of cortisol that suppresses the zero-order production rate by 50% (0.37 vs. 0.11 ng/ml; p 0.05), suggesting a decreased sensitivity to the effects of methylprednisolone on cortisol suppression. OC users experienced a greater net suppression of basophils at drug effect than at baseline. Methylprednisolone appeared to have no effect on helper T-cell responses. These findings suggest that OCs inhibit methylprednisolone metabolism. Since there were inconsistent changes in several responses, women can likely receive similar doses of methylprednisolone irrespective of OC use.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Anti-Inflammatory Agents / pharmacokinetics*
  • Contraceptives, Oral, Hormonal / pharmacology*
  • Cross-Over Studies
  • Female
  • Histamine / blood
  • Humans
  • Hydrocortisone / blood
  • Immunosuppressive Agents / pharmacokinetics*
  • Lymphocyte Count
  • Methylprednisolone / pharmacokinetics*
  • Reference Values


  • Anti-Inflammatory Agents
  • Contraceptives, Oral, Hormonal
  • Immunosuppressive Agents
  • Histamine
  • Hydrocortisone
  • Methylprednisolone