Most of the EPA in the plasma is incorporated in phospholipids, TGs, and cholesteryl MM-102 molecular weight esters; <1 % of the total EPA is unesterified . EPA is metabolized mainly by beta oxidation with cytochrome P450 (CYP)-mediated metabolism as a minor pathway of elimination . No clinically significant pharmacokinetic (PK) drug–drug interactions have been Pictilisib nmr observed with the CYP3A4, CYP2C8, and CYP2C9 substrates atorvastatin, rosiglitazone, and warfarin, respectively . Omeprazole is a proton pump inhibitor that is widely used for the treatment of duodenal and gastric ulcers, gastroesophageal
reflux disease (GERD), and erosive esophagitis [7, 8]. CYP2C19 is the principal enzyme involved in the metabolism of several proton pump inhibitors [9, 10]. There are differences in the activity of CYP2C19 in different individuals, and omeprazole PK profiles may be influenced by CYP2C19 polymorphisms [10, 11]. Omeprazole is a highly sensitive competitive substrate of CYP2C19, and is recommended in FDA guidance for use as a probe
in drug–drug interaction studies in humans . The objective of this study was to investigate LY2874455 mouse the effect of IPE 4 g/day on the plasma PK of orally administered omeprazole 40 mg/day and the potential for a drug–drug interaction. 2 Methods 2.1 Study Population Healthy non-smoking men and women >18 and <55 years of age were eligible if they had a body mass index (BMI) >18 and ≤35 kg/m2 and were in good health as determined by medical history and medical examination. Tideglusib Women of childbearing potential were required to use an acceptable method of birth control, and were excluded if they were pregnant, nursing, or planning a pregnancy. All medications or dietary supplements with known or potential lipid-altering effects (including statins, niacin >200 mg/day, fibrates, ezetimibe, bile acid sequestrants, or medications, supplements or foods enriched with omega-3 fatty acids) were prohibited within 4 weeks prior to the first dose of study medication and until the end of the study. Subjects were required to discontinue consumption
of fish or foods fortified with EPA and/or docosahexaenoic acid at least 1 week prior to the first dose. Use of any medication that could change plasma lipid fractions or affect EPA concentrations in these fractions was disallowed. Subjects who routinely used omeprazole or any other H+/K+ ATPase inhibitors or antacids within 4 weeks prior to the beginning of the study were excluded. 2.2 Study Design This single-center, open-label, phase I study used a crossover design to investigate possible drug–drug interactions between IPE at steady state and two different drugs metabolized by CYP2C class isozymes, omeprazole (CYP2C19) and rosiglitazone (CYP2C8). During a 28-day screening period, healthy adults were evaluated for eligibility and clinical laboratory testing was completed.