Pharmacokinetic Interaction between Atorvastatin and Omega-3 Fatty Acid in Healthy Volunteers

Abstract

The interaction between statins and omega-3 fatty acids remains controversial. The aim of this phase 1 trial was to evaluate the pharmacokinetics of drug-drug interaction between atorvastatin and omega-3 fatty acids. Treatments were once-daily oral administrations of omega-3 (4 g), atorvastatin (40 mg), and both for 14 days, 7 days, and 14 days, respectively, with washout periods. The concentrations of atorvastatin, 2-OH-atorvastatin, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) were determined with LC-MS/MS. Parameters of DHA and EPA were analyzed after baseline correction. A total of 37 subjects completed the study without any major violations. The geometric mean ratios (GMRs) and 90% confidence intervals (CIs) of the co-administration of a single drug for the area under the concentration–time curve during the dosing interval at steady state of atorvastatin, 2-OH-atorvastatin, DHA, and EPA were 1.042 (0.971–1.118), 1.185 (1.113–1.262), 0.157 (0.091–0.271), and 0.557 (0.396–0.784), respectively. The GMRs (90% Cis) for the co-administration at steady state of atorvastatin, 2-OH-atorvastatin, DHA, and EPA were 1.150 (0.990–1.335), 1.301 (1.2707–1.1401), 0.320 (0.243–0.422), and 0.589 (0.487–0.712), respectively. The 90% CIs for most primary endpoints were outside the range of typical bioequivalence, indicating a pharmacokinetic interaction between atorvastatin and omega-3.

A Randomized, Open-Label, Single-Dose, Crossover Study of the Comparative Bioavailability of EPA and DHA in a Novel Liquid Crystalline Nanoparticle-Based Formulation of ω-3 Acid Ethyl Ester Versus Omacor® Soft Capsule among Healthy Adults

“…As a result, ω-3 fatty acid absorption was increased much more as compared to the commercialized cap Omacor ® . An investigation of the metabolic fate of EPA and DHA revealed that DHA metabolism remained substantially unchanged following stomach oxidation, enhancing DHA bioavailability in comparison to EPA [4,21].…”

“…In the age of modern medication, high-intensity statins are often recommended as a first-line treatment for hyperlipidemia in reducing LDL-C levels. These statins are potent cholesterol-lowering drugs that have demonstrated effectiveness in lowering LDL-C levels and reducing the risk of cardiovascular incidents [4]. However, it is essential to acknowledge that statins also come with potential risks and side effects.…”

Evaluating the effect of atorvastatin exposure and vitamin D levels on lipid outcomes in people with HIV‐1 with suppressed HIV‐1 RNA and LDL cholesterol <130 mg/dL

“…Atorvastatin trough concentrations (therapeutic range for trough 1.0 ± 0.7 ng/mL after a dose of 40 mg) for the active parent drug were obtained 20 weeks after initiation of active atorvastatin treatment [11]. Participants were required to delay their daily atorvastatin dose on this visit until after the blood draw, approximately 24 h after the prior dose, and reported the time of their last atorvastatin dose.…”

Pharmacokinetic Comparison Between a Fixed-Dose Combination of Atorvastatin/Omega-3-Acid Ethyl Esters and the Corresponding Loose Combination in Healthy Korean Male Subjects

“…Inc., Korea) was developed to improve compliance and convenience. While the possibility of drug interactions between atorvastatin and omega-3-acid ethyl esters has been reported, 13 the efficacy and safety of ATMEG CombiGel have been confirmed through a Phase 3 study. 14 The FDC formulation of atorvastatin and omega-3-acid ethyl esters contains atorvastatin tablet inside the omega-3-acid ethyl esters capsule.…”