Effect of pradigastat, a diacylglycerol acyltransferase 1 inhibitor, on the pharmacokinetics of a combination oral contraceptive in healthy female subjects

Objective: We evaluated the potential pharmacokinetic interaction between pradigastat, a potent and selective dia-cylglycerol acyltransferase 1 inhibitor, and Levora-28®, a combination oral contraceptive (COC) containing 30 μg ethinylestra-diol (EE) and 150 μg levonorgestrel (LVG). Methods: An open-label, single-sequence, three-period (period 1, single dose of COC; period 2, pradigastat 100 mg × 3 days followed by 40 mg × 7 days; and period 3, both pradigastat 40 mg and a single dose of COC) study involving 24 healthy female subjects of childbearing potential was conducted. Results: The pharmacokinetic parameters of EE were similar when administered alone or in combination with pradigastat, as the 90% confidence interval (CI) of geometric mean ratios for EE exposure (AUC and Cmax) were all within the range of 0.80 - 1.25. The AUC∞, AUClast, and Cmax of LVG were slightly increased in the presence of pradi-gastat, the geometric mean ratios (90% CI) were 1.25 (1.16, 1.35), 1.24 (1.15, 1.34), and 1.16 (1.06, 1.27), respectively. Conclusions: Pradigastat did not elicit clinically relevant changes in the magnitude of Levora-28® exposure. Therefore, dose adjustment is not required for Levora-28® when co-administered with pradigastat