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

Abstract

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 (AUCτ) 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 (AUC_τ, 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 (AUC_τ, 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.

Keywords::

• atorvastatin
• bioavailability
• pharmacokinetics
• prescription omega-3-acid ethyl esters

Acknowledgements

Help with manuscript preparation was provided by Mini Balaram MD, Courtney Breuel and Ruth Kostik Grossman MA, who are employees of DesignWrite LLC, Princeton, New Jersey.

These data were presented at the Annual Meeting of the American College of Clinical Pharmacy (ACCP) at Denver, Colorado on 14 – 17 October 2007.