Pharmacokinetics of dipfluzine hydrochloride in Beagle dogs after single intravenous dose / 中国药理学通报

ABSTRACT

Aim To investigate the pharmacokinetics of dipfluzine hydrochloride,a novel piperazines calcium antagonist.Methods Eighteen Beagle dogs were randomly divided into three groups,which were administered with dipfluzine hydrochloride at iv single dose of 1.5,3.0 and 6.0 mg?kg-1,respectively.The blood was collected at different time.A RP-HPLC method was developed to determine the concentration of dipfluzine hydrochloride in plasma.The pharmacokinetic parameters were calculated by 3P97 software.Results The specificity,lowest limit of detection and quantification,extraction recoveries,the precision of intra-and inter-day and stability were qualified to the pharmacokinetic study.The concentration-time courses of dipfluzine hydrochloride were best fitted to a two-compartment open model at three doses.The main pharmacokinetic parameters at three doses were 24.7,24.2 and 29.6 h for T12?,0.44,1.12 and 2.86 g?min?L-1 for AUC,1.30,1.22 and 1.28 L?kg-1 for Vc,and 3.4?10-3,2.7?10-3 and 2.1?10-3 L?kg-1?min-1 for CL,respectively.Conclusions The developed RP-HPLC method for determination of dipfluzine hydrochloride in plasma can satisfy the requirement of pharmacokinetic study after iv dipfluzine hydrochloride.Analysis of plasma concentration-time curves indicates a biphasic decrease.There was a linear relationship between AUC and dosage.