Icosapent ethyl - How It Works
Clinical pharmacology details from the US FDA-approved label: how Icosapent ethyl works in your body, how it's absorbed, how long it stays active, and how it's eliminated.
Mechanism of Action
12.1 Mechanism of Action Studies suggest that EPA reduces hepatic very low-density lipoprotein triglycerides (VLDL-TG) synthesis and/or secretion and enhances TG clearance from circulating VLDL particles. Potential mechanisms of action include increased β-oxidation; inhibition of acyl-CoA:1,2-diacylglycerol acyltransferase (DGAT); decreased lipogenesis in the liver; and increased plasma lipoprotein lipase activity.
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Studies suggest that EPA reduces hepatic very low-density lipoprotein triglycerides (VLDL-TG) synthesis and/or secretion and enhances TG clearance from circulating VLDL particles.
Potential mechanisms of action include increased β-oxidation; inhibition of acyl-CoA:1,2-diacylglycerol acyltransferase (DGAT); decreased lipogenesis in the liver; and increased plasma lipoprotein lipase activity.
12.2 Pharmacodynamics In a 12-week, dose-ranging study in patients with severe hypertriglyceridemia, icosapent ethyl capsules 4 grams per day reduced median TG from baseline relative to placebo [see Clinical Studies ] .
12.3 Pharmacokinetics Absorption After oral administration, icosapent ethyl is de-esterified during the absorption process and the active metabolite EPA is absorbed in the small intestine and enters the systemic circulation mainly via the thoracic duct lymphatic system.
Peak plasma concentrations of EPA were reached approximately 5 hours following oral doses of icosapent ethyl.
Icosapent ethyl capsules were administered with or following a meal in all clinical studies; no food effect studies were performed.
Take icosapent ethyl capsules with or following a meal.
Distribution The mean volume of distribution at steady state of EPA is approximately 88 liters.
The majority of EPA circulating in plasma is incorporated in phospholipids, triglycerides and cholesteryl esters, and <1% is present as the unesterified fatty acid.
Greater than 99% of unesterified EPA is bound to plasma proteins.
Elimination Metabolism EPA is mainly metabolized by the liver via beta-oxidation similar to dietary fatty acids.
Beta oxidation splits the long carbon chain of EPA into acetyl Coenzyme A, which is converted into energy via the Krebs cycle.
Cytochrome P450-mediated metabolism is a minor pathway of elimination of EPA.
Excretion The total plasma clearance of EPA at steady state is 684 mL/hr.
The plasma elimination half-life (t 1/2 ) of EPA is approximately 89 hours.
Icosapent ethyl does not undergo renal excretion.
Specific Populations Gender When administered icosapent ethyl in clinical trials, plasma total EPA concentrations did not differ significantly between men and women.
Pediatric The pharmacokinetics of icosapent ethyl have not been studied in pediatric patients.
Hepatic or Renal Impairment Icosapent ethyl has not been studied in patients with renal or hepatic impairment.
Drug Interaction Studies Omeprazole In a drug-drug interaction study with 28 healthy adult subjects, icosapent ethyl 4 g/day at steady-state did not significantly change the steady-state AUC τ or C max of omeprazole when co-administered at 40 mg/day to steady-state.
Pharmacokinetics
12.3 Pharmacokinetics Absorption After oral administration, icosapent ethyl is de-esterified during the absorption process and the active metabolite EPA is absorbed in the small intestine and enters the systemic circulation mainly via the thoracic duct lymphatic system. Peak plasma concentrations of EPA were reached approximately 5 hours following oral doses of icosapent ethyl. Icosapent ethyl capsules were administered with or following a meal in all clinical studies; no food effect studies were performed. Take icosapent ethyl capsules with or following a meal. Distribution The mean volume of distribution at steady state of EPA is approximately 88 liters. The majority of EPA circulating in plasma is incorporated in phospholipids, triglycerides and cholesteryl esters, and <1% is present as the unesterified fatty acid. Greater than 99% of unesterified EPA is bound to plasma proteins. Elimination Metabolism EPA is mainly metabolized by the liver via beta-oxidation similar to dietary fatty acids. Beta oxidation splits the long carbon chain of EPA into acetyl Coenzyme A, which is converted into energy via the Krebs cycle. Cytochrome P450-mediated metabolism is a minor pathway of elimination of EPA. Excretion The total plasma clearance of EPA at steady state is 684 mL/hr. The plasma elimination half-life (t 1/2 ) of EPA is approximately 89 hours. Icosapent ethyl does not undergo renal excretion. Specific Populations Gender When administered icosapent ethyl in clinical trials, plas