Effect of Multiple Oral Doses of Linagliptin on the Steady-State Pharmacokinetics of a Combination Oral Contraceptive in Healthy Female Adults

Methods: This was an open-label, two-period, fixed-sequence, multiple-dose study, consisting of a run-in period, a 14-day reference treatment period and a 7-day test treatment period. The study recruited 18 healthy pre-menopausal female subjects aged 18–40 years with a body mass index of 18.5–27.0 kg/m². Only women with regular menstrual cycles were included in this study. The treatment sequence was divided into three steps: an individually tailored run-in period with EE 30 µg/LNG 150 µg to synchronize the menstrual cycles of the subjects followed by a washout period of 7 days; the reference treatment period, during which EE 30 µg/LNG 150 µg alone was taken on days 1–14; and the test treatment period, during which EE 30 µg/LNG 150 µg plus linagliptin were taken on days 15–21. The pharmacokinetic parameters measured were maximum steady-state plasma concentration during a dosage interval (C_max,ss), time to reach maximum plasma concentration following administration at steady state (t_max,ss) and area under the plasma concentration-time curve during a dosage interval (τ) at steady state (AUC_τ,ss).

Results: The AUC_τ,ss and C_max,ss of EE and LNG were comparable when EE 30 µg/LNG 150 µg was given alone or combined with linagliptin. The adjusted geometric mean ratios for AUC_τ,ss and C_max,ss of EE following EE 30 µg/LNG 150 µg plus linagliptin versus EE 30 µg/LNG 150 µg alone were 101.4 (90% CI 97.2, 105.8) and 107.8 (90% CI 99.7, 116.6), respectively. The adjusted geometric mean ratios for AUC_τ,ss and C_max,ss of LNG following EE 30 µg/LNG 150 µg plus linagliptin versus EE 30 µg/LNG 150 µg alone were 108.8 (90% CI 104.5, 113.3) and 113.5 (90% CI 106.1, 121.3), respectively. The combination was well tolerated.