Pharmacokinetic interaction between anlotinib and amlodipine besylate in rats

The aim of this study was to evaluate the pharmacokinetic interaction between anlotinib and amlodipine besylate after single and multiple administrations in rats. Sprague-Dawley (SD) rats were randomly divided into three groups: anlotinib group, amlodipine besylate group, and combination (anlotinib + amlodipine besylate) group. The anlotinib group received anlotinib at 6 mg/kg via oral gavage, the amlodipine besylate group received amlodipine besylate at 4 mg/kg via oral gavage, and the combination group received both anlotinib (6 mg/kg) and amlodipine besylate (4 mg/kg) simultaneously via oral gavage. Plasma concentrations of anlotinib and amlodipine were determined using a validated LC-MS/MS method. Mean plasma concentration-time curves were plotted, and pharmacokinetic parameters were calculated using non-compartmental modeling. Compared with the amlodipine group, Cmax and AUC0−t of amlodipine in the combination group increased to 2.34-fold and 2.01-fold, respectively, and CL decreased by 64.4% after single-dose administration (P < 0.05). After multiple-dose administration, AUC0−∞ and t1/2 increased to 3.30-fold and 2.73-fold, respectively, and clearance decreased by 64.9% (P < 0.05). The pharmacokinetic parameters of anlotinib were not significantly changed by co-administration with amlodipine (P > 0.05). Co-administration of anlotinib and amlodipine significantly increased the systemic exposure to amlodipine. Therefore, potential drug–drug interactions should be considered when these drugs are co-administered in clinical practice to ensure safe and rational medication use.