ABT-335, the choline salt of fenofibric acid, does not have a clinically significant pharmacokinetic interaction with rosuvastatin in humans.

ABT-335 is the choline salt of fenofibric acid under clinical development as a combination therapy with rosuvastatin for the management of dyslipidemia. ABT-335 and rosuvastatin have different mechanisms of actions and exert complementary pharmacodynamic effects on lipids. The current study assessed the pharmacokinetic interaction between the 2 drugs following a multiple-dose, open-label, 3-period, randomized, crossover design. Eighteen healthy men and women received 40 mg rosuvastatin alone, 135 mg ABT-335 alone, and the 2 drugs in combination once daily for 10 days. Blood samples were collected prior to dosing on multiple days and up to 120 hours after day 10 dosing for the measurements of fenofibric acid and rosuvastatin plasma concentrations. Coadministering 40 mg rosuvastatin had no significant effect on the steady-state Cmax, Cmin, or AUC24 of fenofibric acid (P > .05). Coadministering ABT-335 had no significant effect on the steady-state Cmin or AUC24 of rosuvastatin (P > .05) but increased Cmax by 20% (90% confidence interval: 12%-28%). All 3 regimens were generally well tolerated with no clinically significant changes in clinical laboratory values, vital signs, or electrocardiograms during the study. Results from this study demonstrate no clinically significant pharmacokinetic interaction between ABT-335 at the full clinical dose and rosuvastatin at the highest approved dose.

The effects of multiple doses of fenofibrate on the pharmacokinetics of pravastatin and its 3alpha-hydroxy isomeric metabolite.

Published data indicate that coadministration of multiple doses of the fibrate drug, gemfibrozil, led to a 202% increase in pravastatin systemic exposure (area under the plasma concentration-time curve, AUC). To evaluate the effects of another fibrate drug, fenofibrate, on the pharmacokinetics of pravastatin, 24 healthy subjects took pravastatin (40 mg once daily) on study days 1 to 15 and fenofibrate (160 mg once daily) on study days 6 to 15. Blood samples were collected for 24 hours after dosing on days 5, 6, and 15. Plasma concentrations of pravastatin and its active metabolite, 3alpha-hydroxy-iso-pravastatin, were measured, and pharmacokinetics was assessed. Safety assessments were based on adverse events, physical examinations, electrocardiogram results, vital signs, and clinical laboratory testing. Safety results were unremarkable. Coadministration of fenofibrate had modest effects on pravastatin and 3alpha-hydroxy-iso-pravastatin systemic exposures (AUC). Increases in pravastatin systemic exposures (19%-28%, on average) and 3alpha-hydroxy-iso-pravastatin systemic exposures (24%-39%, on average) were observed upon coadministration, but individual changes were variable. Pravastatin and 3alpha-hydroxy-iso-pravastatin systemic exposures were not statistically significantly different following the 1st and 10th doses of fenofibrate.