Pharmacokinetics and bioequivalence of two fenofibrate choline formulations in healthy subjects under fed and fasted condition

摘要

Objective: The objective of this study was to evaluate the pharmacokinetics and biocquivalence of two formulations (the original capsule ("reference") and the new tablet ("test") formulations) of 135-mg choline fenofibrate under fed and fasted conditions. Materials and methods; This was an open-label, randomized, single-dose, crossover bioequivalencc study in healthy Korean males. A total of 40 individuals were separately enrolled in the high-fat fed and the fasting study, respectively, and were randomized in a 1:1 ratio into two sequences. Serial blood samples were collected over 72 hours after dnig administration. Plasma concentrations of fenofibric acid were determined by a validated LC-MS/MS method. Phannacokinetic (PK) parameters were estimated using noncompartmental methods. Results: Overall, 37 and 35 individuals completed the fed and the fasting study, respectively, as planned. The estimated C-ma(x), AUC(0-infinity) and AUC(0-last) were comparable between the test and the reference formulations in both fed and fasting studies (p > 0.05). The 90% confidence intervals for the geometric mean ratios of C-ma(x), AUC(0-infinity) and AUC(0-last) were 0.92 -1.06, 0.95 -1.01, and 0.95 - 1.01 in the fed study; and 0.94 - 1.12, 0.94 - 1.00, and 0.94 - 1.00 in the fasting study, respectively. For both formulations, t(max) was significantly prolonged under fed condition compared to fasting condition (p 0.05). Conclusion: The reference and the test formulations of 135 mg choline fenofibrate show comparable pharmacokinetic profiles of fenofibric acid under both fed and fasted conditions and are considered bioequivalent.