Effect of troglitazone on the pharmacokinetics of an oral contraceptive agent

Fifteen healthy women participated in a study to determine the effect of mu ltiple doses of troglitazone on the pharmacokinetics of Ortho-Novum 1/35 (3 5 mu g ethinyl estradiol [EE] and 1 mg norethindrone [NE]). Participants re ceived three cycles (21 days each of active drug followed by 7 days without medication) of Ortho-Novum. During the third cycle, participants also rece ived troglitazone 600 mg qd for 22 days. Pharmacokinetic profiles of EE and NE were determined on day 21 of the second and third cycles. Progesterone and sex hormone binding globulin (SHBG) levels were also measured. Troglita zone decreased EE C-max and AUC((0-24)) by 32% and 29%, respectively. Likew ise, troglitazone decreased NE C-max and AUC((0-24)) by 31% and 30%, respec tively. Plasma SHBG concentrations increased from 113 nmol/L during cycle 2 to 220 nmol/L during cycle 3. Troglitazone reduced plasma unbound AUC for NE by 49%. Serum progesterone levels were lower than 1.5 ng/mL on all occas ions. Thus, coadministration of troglitazone and Ortho-Novum decreases the systemic exposure to EE and NE. A higher dose of oral contraceptive or an a lternate method of contraception should be considered for patients treated with troglitazone. (C) 1999 the American College of Clinical Pharmacology.