复方烟酸双层缓释片与市售烟酸缓释片的生物等效性研究

目的:研究复方烟酸双层缓释片和市售烟酸缓释片的生物等效性。方法:采用双周期自身交叉给药,6只家犬单剂量灌胃复方烟酸双层缓释片与市售烟酸缓释片(均含烟酸500 mg)后,采用高效液相色谱法测定给药后12 h内的烟酸血药浓度,以3p97软件计算烟酸药动学参数和相对生物利用度。结果:家犬口服复方烟酸双层缓释片和市售烟酸缓释片后,烟酸的药动学特征符合一室模型;其主要药动学参数tmax分别为(5.2±1.4)、(5.0±1.6)h,cmax分别为(77.3±10.8)、(76.3±7.3)μg/ml,t1/2分别为(1.5±0.2)、(1.4±0.2)h,AUC0-∞分别为(416.6±60.5)、(377.5±50.7)μg·h/ml;双层缓释片的相对生物利用度为(111.1±14.8)%,双层缓释片cmax、AUC0-∞的90%置信区间分别为87.0%¹19.0%、101.0%119.0%、101.0%¹20.0%。结论:两种缓释片的cmax、AUC0-∞比较差异无统计学意义,具有生物等效性。

Bioequivalence Study of Compound Nicotinic Acid Bilayer Sustained-release Tablets and Marketed Nicotinic Acid Sustained-release Tablets

OBJECTIVE： To study the bioequivalence of Compound nicotinic acid （NA） bilayer sustained-release tablets and marketed NA sustained-release tablets. METHODS： A single dose of Compound NA bilayer sustained-release tablets （containing 500 mg NA） and the marketed NA sustained release tablets （containing NA 500 mg） were administered to 6 dogs, respectively, according to the double periods and randomized crossover design. Blood concentration of NA was determined by HPLC within 12 h after medication. The pharmacokinetic parameters and relative bioavailability of NA were calculated with 3p97 software. RESULTS ： The pharmacokinetic characteristics followed one-compartment model after oral administration of Compound NA bilayer sustained-release tablets and NA sustained-release tablets. Their main pharmacokinetie parameters were as follows： tmax were （5.2 ± 1.4） h and （5.0± 1.6） h; cmax, were （77.3± 10.8） μg/ml and （76.3±7.3） μg/ml; t1/2 were （1.5±0.2） h and （1.4±0.2） h; AUC0-∞ were （416.6 ± 60.5） μg·h/ml and （377.5 ± 50.7） μg·h/ml, respectively. The relative bioavailability of Compound NA bilayer sustained-release tablets was （111.1 ± 14.8）%. 90% CI of cmax and AUC0-∞ of Compound NA bilayer sustained-release tablets were 87.0%- 119.0% and 101.0%-120.0%. CONCLUSIONS： The difference of Cmax and AUC0-∞ between 2 kinds of sustained-release tablets has no statistical significance; the 2 kinds of sustained-release tablets are bioequivalent.