Vayarin

Phospholipids can break down into various substrates or remain intact and absorbed in the circulatory system and cross the blood brain barrier. Following dietary ingestion of PS, fatty acids esterified to the PS molecule are hydrolyzed by pancreatic enzymes, forming lyso-PS and free fatty acids (FFA). After the lyso-PS is absorbed by the intestinal mucosa, it can be re-acylated into PS, while partially converted into other phospholipids. Phosphatidylserine and other phospholipids formed inside the enterocytes can either be transported in the lymphatic circulation as chylomicrons or in the hepatic circulation, and enter the systemic circulation for distribution across the body. Current evidence shows that ingested phosphatidylserine reaches the systemic circulation and is incorporated into the phospholipids pool as phosphatidylethanolamine and other metabolites L1506, L1510. The omega-3 polyunsaturated fatty acid metabolism cycle begins with a series of desaturation, elongation and ?-oxidation reactions. In a study of healthy volunteers and patients with hypertriglyceridemia, eicosapentaenoic acid, and DHA were absorbed when administered as ethyl esters orally. Omega-3-acids administered as ethyl esters (Vayarin) induced significant, dose-dependent increases in serum phospholipid eicosapentaenoic acid content, though increases in DHA content were less significant and not dose-dependent when administered as ethyl esters. Uptake of EPA and DHA into serum phospholipids in subjects treated with Vayarin was independent of age (<49 years versus ?49 years). Females were found to have more uptake of EPA into serum phospholipids than males ^L1503. The effect of a mixture of free fatty acids (FFA), EPA/DHA and their FFA-albumin conjugate on cytochrome P450-dependent monooxygenase activities was assessed in human liver microsomes. At the 23 ?M concentration, FFA resulted in a less than 32% inhibition of CYP1A2, 2A6, 2C9, 2C19, 2D6, 2E1, and 3A. At the 23 ?M concentration, the FFA-albumin conjugate resulted in a less than 20% inhibition of CYP2A6, 2C19, 2D6, and 3A, with a 68% inhibition being seen for CYP2E1 ^L1503. In healthy volunteers and in patients with hypertriglyceridemia (HTG), EPA and DHA were absorbed when administered as ethyl esters orally. Omega-3-acids administered as ethyl esters (Vayarin) induced significant, dose–dependent increases in serum phospholipid EPA content, though increases in DHA content were less marked and not dose-dependent when administered as ethyl esters. Uptake of EPA and DHA into serum phospholipids in subjects treated with Vayarin was independent of age (<49 years vs. ?49 years). Females tended to have more uptake of EPA into serum phospholipids than males. Pharmacokinetic data on Vayarin in children are not available L1506, L1508.

For all routes of administration, about 60% of the ingested PS is excreted in feces, while 10% is eliminated in the urine ^L1506.