Acipimox Pharmacokinetics And Drug Interactions

Objective: A HPLC-UV method with detection was developed and validated to determine Acipimox in human plasma. To study the pharmacokinetics profiles and bioequivalence of Acipimox in healthy Chinese volunteers. To assess the pharmacokinetics profiles of single Acipimox and combined with Gemfibrozil in rabbits. Methods: 250 mg single oral dose of domestic and imported Acipimox capsules were given tol 8 healthy volunteers in an open randomized crossover. 8 rabbits were divided into Acipimox groups and Acipimox in combination with Gemfibrozil groups. Acipimox concentrations in plasma of healthy volunteers and rabbits were determined by HPLC method. The pharmacokinetics parameters as well as relative bioavailability were measured. To compare the difference of two groups and realize the case of drug interactions under the condition of combination with otherdrugs. Results: the concentration-time curves of domestic and imported Acipimox capsules were conformed to an one-compartment open model with first- order absorption, fitst-order elimination from the central compartment. the main pharmacokinetic parameters of domestic or imported preparations were as follows: Cmax were 3.58?.85 and 3.74?.94 mg/L; Tmax were 1.89?.58 and 1.94?.73 h; were , 0-12 were 15.97?.15 and 16.17?.15 Tl/2ke 1.94?.24 and 1.99?.19 h AUC mg hlL respectively. There were no significant different between the two formulations (P>0.05). the relative bioavailability of domestic Acipimox capsule was 99 ?14 %. The pharmacokinetics parametres of combination groups and single groups of rabbits were as follow: TII2ke were 2.19+0.14 and 1.23?.12 h; AUC0~ were 7.20?.24 and 6.37?.24 mg hIL; CL/F were 6.68?.55 and 10.30+1.36 L/h. There were significant different between the two groups (P<0.05). The excretion process of Acipimox was disturbed by Gemfibrozil possibly. Conclusion: A HPLC-UV method that determine Acipimox in plasma is simple, sensitive and accurate. It will provide a scientific basis for the pharmacokinetics studes of Acipimox.The pharmacokinetics parametres of Acipimox provide refences for rational clinical application of Acipimox. Domestic and imported Acipimox capsules were bioequivalent. The excretion process of Acipimox in rabbits was prolonged by co- administered drugs.