Pharmacokinetics and bioequivalence of two fenofibrate choline formulations in healthy subjects under fed and fasted condition\u2029.

Abstract

OBJECTIVE\nThe objective of this study was to evaluate the pharmacokinetics and bioequivalence of two formulations (the original capsule ( reference ) and the new tablet ( test ) formulations) of 135-mg choline fenofibrate under fed and fasted conditions.\n\n\nMATERIALS AND METHODS\nThis was an open-label, randomized, single-dose, crossover bioequivalence 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\xa0hours after drug administration. Plasma concentrations of fenofibric acid were determined by a validated LC-MS/MS method. Pharmacokinetic (PK) parameters were estimated using noncompartmental methods.\n\n\nRESULTS\nOverall, 37 and 35 individuals completed the fed and the fasting study, respectively, as planned. The estimated Cmax, AUC0-∞, and AUC0-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 Cmax, AUC0-∞, and AUC0-last were 0.92\xa0-\xa01.06, 0.95\xa0-\xa01.01, and 0.95\xa0-\xa01.01 in the fed study; and 0.94\xa0-\xa01.12, 0.94\xa0-\xa01.00, and 0.94\xa0-\xa01.00 in the fasting study, respectively. For both formulations, tmax was significantly prolonged under fed condition compared to fasting condition (p < 0.0001); all other PK parameters were comparable between the fed and the fasting studies (p > 0.05).\n\n\nCONCLUSION\nThe 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.\u2029.