洛伐他汀缓释片在Beagle犬体内的药动学特性与生物等效性

Bioequivalence and pharmacokinetic characteristics of lovastatin sustained release tablets in Beagle dogs

目的:研究洛伐他汀缓释片在Beagle犬体内的药动学特征及其口服相对生物利用度。方法:Beagle 犬12条随机分为2组,分别单次口服洛伐他汀缓释片和普通片备60 mg,用RP-HPLC法检测血药浓度。药动学参数用3P97软件分析。结果:洛伐他汀缓释片和普通片的tmax分别为(2．7±5 0．8)和(2．8±1．0)h,cmax分别为(137±43)和(176±59)μg·L-1,t1／2分别为(11±4)和(10±5)h;AUC0-(?)分别为(956±146)和(1 005± 147)μg·h·L-1。以AUC0-(?)计算,与普通片相比,洛伐他汀缓释片的相对生物利用度为(95±6)％。洛伐他汀缓释片和普通片AUC0-(?)对数比值的90％可信限为81．6％-112．2％。结论:洛伐他汀缓释片具有一定缓释特性,与普通片相比具有生物等效性。

AIM： To study the oral correlative bioequivalence and pharmacokinetics of lovastatin sustained release tablets in Beagle dogs. METHODS： Twelve Beagle dogs were randomized divided into two groups：A, subjects administered with a single 60 mg oral dose of lovastatin sustained-release tablets and B, lovastatin generic tablets. Plasma lovastatin levels were determined by a reversed-phase HPLC method. The pharmacokinetic parameters were calculated by 3P97 software. RESULTS：The comparison of pharmacokinetic parameters between the two preparations （ lovastatin sustained-release tablets, lovastatin generic tablets） were as follow, tmax,cmax, t1/2 and AUC0-4 were（2.7 ± s 0.8） h, （137 ± 43）μg·L^-1, （11 ± 4） h,and （956 ±146） μg·h·L^-1 for lovastatin sustained-release tablets （group A） vs （2.8±1.0） h,（176 ± 59） μg·L^-1, （10 ± 5） h ,and （1 005 ± 147） μg·h·L^-1respectively for lovastatin generic tablets（group B）. Relative bioavailability of the former was （95 ±6） %.The 90 % confidence interval calculated from log-transformed values was 81.6 %～112.2 % for logarithm ratio of AUC0-4 in two groups. CONCLUSION： Lovastatin sustained-release tablets shows prolonged-action characteristics and possesses bioequivalence with lovastatin generic tablets.