Effect of High-Fat Diet on Pharmacokinetics and Incidence of Adverse Reactions of Tacrolimus in Healthy Chinese Participants

Abstract

The effects of food on the pharmacokinetics (PKs) and safety of 1 mg Tacrolimus sustained-release Tacrolimus capsules in healthy Chinese subjects were investigated from one bioequivalence trial. The bioequivalence trial was designed as single-center, openlabel, randomized, single-dose, two-sequence, four-period crossover under both fasted and fed conditions. A total of 80 healthy subjects were enrolled. These subjects received a single oral 1 mg dose of Tacrolimus with a 14-day washout between four periods. Serial PK samples were collected and blood concentrations were analyzed using validated high-performance liquid chromatography–mass spectrometry. Pharmacokinetic parameters were calculated by noncompartmental methods. The BE module of WinNonLin was used for statistical analysis of the maximum concentration (C_max), the area under the concentration–time curve from zero to the final measurable concentration (AUC_0–t), and the area under the concentration–time curve from time zero to infinity (AUC_0–∞) of Tacrolimus in blood.

The mean values of all pharmacokinetic parameters were similar for the T and R formulations under fasting and fed conditions, and the 90% confidence intervals were inside the 80.00%–125.00% range. For both the T and R formulations, the AUC_0–t and AUC_0–∞ values were higher in the fed test than in the fasting one. The incidence of adverse events (AEs) was similar between the fasted and fed states, and no serious AEs were observed. Fasting significantly increased the exposure of Chinese subjects to 1 mg Tacrolimus.