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

Abstract

Background: Patients with persistent hypertriglyceridemia while on statin therapy may require adjunctive lipid-lowering therapy to meet treatment goals. Objective: To assess the effect of concomitant administration of prescription ω-3-acid ethyl esters (P-OM3), triglyceride-lowering agents, on the steady-state pharmacokinetics of rosuvastatin. Methods: A randomized, open-label, repeated-dose, two-way crossover drug interaction study of two treatments – 4 g P-OM3 plus 40 mg rosuvastatin or 40 mg rosuvastatin alone administered daily for 14 days each under fasting conditions – was conducted in 48 non-smoking healthy adults. Main outcome measures: The primary determinants of drug interaction were the ln-transformed area under the plasma concentration versus time curve [AUC_t(ss)] over the final (day 14) 24 h dosing interval and maximum measured steady-state plasma rosuvastatin concentration [C_max(ss)] on day 14. Safety was assessed by clinical and laboratory testing and recording of adverse events. Results: AUC_t(ss) and C_max(ss) following daily administration of rosuvastatin with P-OM3 were similar to those following monotherapy with rosuvastatin. All adverse events recorded during the study were classified as mild and self-limited. Conclusions: Administration of P-OM3 with rosuvastatin did not affect the pharmacokinetics of rosuvastatin under steady-state conditions in healthy individuals.

Keywords::

• pharmacokinetics
• prescription omega-3-acid ethyl esters
• rosuvastatin
• steady state

Acknowledgements

Support for manuscript preparation was provided by Mini Balaram MD and Vaishali Soni RPh PharmD, who are employees of DesignWrite LLC, Princeton, NJ.