Effects of diet and gender on the pharmacokinetics of oral lenvatinib: A clinical trial in healthy Chinese participants

Objective: Lenvatinib is a tyrosine kinase inhibitor that helps prevent angiogenesis. In this study, we investigated the potential influencing factors on lenvatinib pharmacokinetics to provide a reference for clinical application. Materials and methods: All healthy participants received a single dose of 4 mg lenvatinib mesylate capsules with a high-fat meal or fasted conditions. Lenvatinib plasma concentrations were determined via high-performance liquid chromatography-mass spectrometry/mass spectrometry, and the pharmacokinetic parameters were calculated using WinNonlin 8.1 software. A mixed effect model analysis was adopted to explore the influence factor for the pharmacokinetic parameters of lenvatinib. Results: After a single oral dose of 4 mg lenvatinib mesylate, the pharmacokinetic parameters for the fasted and fed groups were as follows: t(max) was 2.0 hours and 4.5 hours, C-max was 53.60 ng/mL and 45.54 ng/mL, AUC(0- t) was 597.44 hxng/mL and 561.51 hxng/mL, CL was 6.82 L/h and 7.26 L/h, and Vd was 82.82 L and 94.04 L, respectively. Compared with those in the fasted group, decreased Cmax and increased tmax were observed in the fed group. The geometric mean ratios of fed/fasted for C-max, AUC(0-t), and AUC(0-infinity) were 86.9%, 94.0%, and 93.9%, respectively, and the pharmacokinetics of lenvatinib were significantly influenced by food intake. Gender influenced the pharmacokinetics of lenvatinib; femaleshad higher Cmax and AUC(0- t) levels after 4 mg lenvatinib. Lenvatinib was well tolerated in healthy Chinese subjects. Conclusion: Highfat diet altered the pharmacokinetic profile of lenvatinib, but not sufficient to significantly impact its clinical efficacy. Therefore, lenvatinib is suitable for administration under fasted or fed conditions.