Pharmacokinetics of nitrendipine pellets in healthy dogs

OBJECTIVE To study the pharmacokinetics of nitrendipine immediate-release and sustained-release pellets,and evaluate the relative bioavailability in dogs.METHODS Following oral administration of a single dose of the nitrendipine immediate-release and sustained-release pellets as test formulations,and domestic tablets and Japanese tablets as reference formulations,drug in plasma was determined by HPLC and the plasma concentration-time curves of these formulations were obtained.The pharmacokinetic parameters were calculated and analyzed by ANOVA,and subsequently the relative bioavailabilities of two test formulations were evaluated.RESULTS The pharmacokinetic parameters of immediate-release pellets,sustained-release pellets,domestic tablets and Japanese tablets of nitrendipine were as below in turn:Tmax were 0.92±0.14,5.0,1.83±0.29 and 1.08±0.38h,respectively.Cmax were 187.01±21.23,85.25±13.80,88.31±8.65 and 160.22±24.34ng·mL-1,respectively.AUC0～t were 665.54±109.07,606.47±130.68,472.44±89.44 and 659.16±100.05ng·h·mL-1,respectively.The relative bioavailabilities of immediate-release pellets and sustained-release pellets were 146.92% and 135.92% compared with domestic tablets.However,the relative bioavailabilities of the two formulations were 101.04% and 91.63% respectively in comparison with Japanese tablets.CONCLUSION The quality of immediate-release nitrendipine pellets was equal to Japanese tablets and prior to the domestic tablets.Compared with two reference formulations,the sustained-release nitrendipine pellets have longer action time in dogs,however,a lower bioavailability was also found,which suggesting that the formulation or processing of the sustained-release pellets should be optimized in future.