Effect of Troglitazone on the Pharmacokinetics of an Oral Contraceptive Agent

15 healthy women participated in a study to determine the effect of multiple doses of troglitazone on the pharmacokinetics of Ortho-Novum 1/35 (35 mcg ethinyl estradiol [EE] and 1 mg norethindrone [NE]). Participants received three cycles (21 days each of active drug followed by 7 days without medication) of Ortho-Novum. During the third cycle participants also received troglitazone at 600 mg 4 times daily 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. Troglitazone decreased EE maximum plasma concentrations (Cmax) and area under plasma concentration (AUC)(0-24) by 32% and 29% respectively. Likewise troglitazone decreased NE Cmax and AUC(0-24) by 31% and 30% respectively. 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 occasions. Thus co-administration of troglitazone and Ortho-Novum decreases the systemic exposure to EE and NE. A higher dose of oral contraceptive or an alternate method of contraception should be considered for patients with troglitazone. (authors)