Effect of omega-3-acid ethyl esters on steady-state plasma pharmacokinetics of atorvastatin in healthy adults.

Author(s): Di Spirito M, Morelli G, Doyle RT, Johnson J, McKenney J

Affiliation(s): MDS Pharma Services, 2350 Cohen Street, Saint-Laurent, Montreal, Quebec, H4R 2N6, Canada. mike.dispirito@mdsinc.com

Publication date & source: 2008-12, Expert Opin Pharmacother., 9(17):2939-45.

Publication type: Randomized Controlled Trial; Research Support, Non-U.S. Gov't

BACKGROUND: Prescription omega-3-acid ethyl esters (P-OM3) have been used as adjunctive therapy to statin drugs in patients with mixed hyperlipidemia. OBJECTIVE: To assess the effect of concomitant administration of 4 g P-OM3 on the steady-state pharmacokinetics of the maximum recommended daily dose of atorvastatin (80 mg) in healthy volunteers. METHODS: This was a randomized, open-label, repeated-dose, two-way crossover, drug interaction study of two treatments: 4 g of P-OM3 with 80 mg atorvastatin daily or 80 mg atorvastatin daily, each administered for 14 days under fasting conditions to 50 healthy adults. Main outcome measures: The primary determinants of drug interaction were the ln-transformed area under the plasma concentration versus time curve (AUCtau) and maximum measured steady-state plasma concentration (C(max,ss)) over the final 24 h dosing interval (day 14) for atorvastatin and 2-hydroxyatorvastatin. Safety assessment included clinical laboratory evaluations and adverse event reporting. RESULTS: The extent and rate of exposure (AUCtau, C(max,ss)) to atorvastatin and its active metabolites following daily administration of P-OM3 with atorvastatin (80 mg) were similar to those following the administration of atorvastatin (80 mg) alone. Both treatments were well tolerated. CONCLUSIONS: After 14 days of dosing, the rate and extent of exposure (AUCtau, C(max,ss)) to atorvastatin and its active metabolites were similar with both treatments, indicating that administration of P-OM3 did not affect the steady-state bioavailability of orally administered atorvastatin.