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 diacylglycerol acyltransferase 1 inhibitor, and Levora-28®, a combination oral contraceptive (COC) containing 30 μg ethinylestradiol (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 x 3 days followed by 40 mg x 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(max)) were all within the range of 0.80 - 1.25. The AUC(∞), AUC(last), and C(max) of LVG were slightly increased in the presence of pradigastat, 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.
Jin
J
Chen
Suraj
S
Bhansali
Srikanth
S
Neelakantham
Craig
C
Trusley
Tapan
T
Majumdar
Sam
S
Rebello
Gangadhar
G
Sunkara
Charles
C
Meyers
D000085:Acetates / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D000631:Aminopyridines / Q000008:administration & dosage* / Q000009:adverse effects; D019540:Area Under Curve; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051048:Diacylglycerol O-Acyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004338:Drug Combinations; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D016912:Levonorgestrel / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008657:Metabolic Clearance Rate; D018570:Risk Assessment; D012307:Risk Factors; D055815:Young Adult
D000085:Acetates; D000631:Aminopyridines; D003277:Contraceptives, Oral, Combined; D004338:Drug Combinations; D004791:Enzyme Inhibitors; C072593:ethinyl estradiol, levonorgestrel drug combination; C000594809:pradigastat; D004997:Ethinyl Estradiol; D016912:Levonorgestrel; C494881:DGAT1 protein, human; D051048:Diacylglycerol O-Acyltransferase