Chen, Jin, Bhansali, Suraj, Neelakantham, Srikanth Raju, Trusley, Craig, Majumdar, Tapan, Rebello, Sam, Sunkara, Gangadhar and Meyers, Charles (2015) Effect of pradigastat, a diacylglycerol acyltransferase 1 inhibitor, on the pharmacokinetics of a combination oral contraceptive in healthy female subjects. International Journal of Clinical Pharmacology and Therapeutics, 53 (4). pp. 317-324. ISSN 0946-1965

Abstract

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 C<inf>max</inf>) were all within the range of 0.80 - 1.25. The AUC<inf>∞</inf>, AUC<inf>last</inf>, and C<inf>max</inf> 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.

Item Type:	Article
Keywords:	Drug-drug interaction Oral contraceptive Pharmaco-kinetics Pradigastat
Date Deposited:	14 Mar 2018 00:45
Last Modified:	25 Jan 2019 00:45
URI:	https://oak.novartis.com/id/eprint/23674