Low-dose apatinib in subjects with renal impairment: A pharmacokinetics study

Abstract

ObjectiveIn patients with renal impairment, we studied apatinib and its major metabolites (M1–1, M1–2, M1–6, and M9–2) for pharmacokinetics. MethodsSubjects with different renal functions were given a single oral dose of apatinib mesylate tablets of 250 mg. Pharmacokinetic samples were collected at 1 hour before dosing,0.25, 0.5, 1, 2, 3, 4, 6, 8, 24, 48, 72, and 96 h after dosing. The pharmacokinetic parameters of apatinib and its major metabolites were calculated by noncompartmental analysis. ResultsComparing PK parameters of the mild or moderate renal impairment group with the healthy group: the geometric mean ratios of maximum observed drug concentration (Cmax), the area under the plasma drug concentration-time curve from time 0 to the final quantifiable time (AUC0-t), and the area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUC0–inf) were all about one. No significant effect of mild and moderate renal impairment on apatinib pharmacokinetics was observed. Mild and moderate renal impairment was also not observed to have a significant effect on the pharmacokinetics of metabolites M1–1, M1–2, and M1–6. However, mild and moderate renal impairment had a certain increase in exposure to the metabolite M9–2. Considering that M9–2 has no inhibitory effect on protein tyrosine kinase, it has no clinical significance. In addition, the proportion of cumulative excretion of apatinib and its major metabolites was small and almost negligible in all three groups of subjects. ConclusionPatients with mild and moderate renal impairment do not need to adjust the dose of apatinib when using low dose (250 mg) apatinib.