愈创木酚甘油醚缓释片在Beagle犬体内的药动学与生物利用度

Study on the bioavailability and pharmacokinetics of guaiphenesin sustained release tablets in Beagle dogs

目的:建立高效液相色谱法(HPLC)测定BeagIe犬血清中愈创木酚甘油醚的浓度,研究愈创木酚甘油醚缓释片在Beagle犬体内的药动学与相对生物利用度。方法:采用HPLC测定6只Beagle犬口服供试品愈创木酚甘油醚缓释片及参比制剂愈创木酚甘油醚普通片后的经时血药浓度,计算主要药动学参数及相对生物利用度,并进行等效性检验。结果:供试品与参比制剂的主要药动学参数分别是:t_(max)为(1.83±0.26)h和(0.92±0.13)h,C_(max)为(4.7±11.6),(7.4±0.7)mg·L^(-1);AUG_(0-T)为(18.4±2.0),(17.3±2.5)mg·h^(-1)·L^(-1),AUG_(0-∞)为(19.8±2.4),(18.4±2.8)mg·h^(-1)·L^(-1)。两制剂间的lnAUG(0-T)及ln AUG_(0-∞)经方差分析和双单侧t检验,表明两制剂具有生物等效性。愈创木酚甘油醚缓释片的相对生物利用度F_(0-T)为(107.1±8.0)%,F_(0-∞)为(108.3±9.0)%。结论:愈创木酚甘油醚缓释片在Beagle犬体内具有缓释效果,与参比制剂愈创木酚甘油醚普通片生物等效。

OBJECTIVE To establish an RP-HPLC method for determination of guaiphenesin and to study the bioavailability and pharmacokinetics of guaiphenesin sustained release tablets in beagle dogs. METHODS Six Beagle dogs were divided into two groups at random and were given test and reference formulation, then the serum was taken at different times and was determined by RP HPLC. The parameters of pharmacokinetic and relative bioavailability and bioequivalent evaluation of two formulations were calculated. RESULTS The parameters of the test and reference formulation： tmax was（ 1. 8± 0. 3）h and（0.92 ±0.13） h,Cmax was（4.7±0.6）mg·L^-1 and（7.4±0.7）mg·L^-1,AUC0-T was（18.4±2.0）mg·L^-1 and（17.3±2.5）mg·L^-1, AUG0-∞ was（19. 8 ±2. 4）mg·L^-1 and（18.4 ±2. 8）mg·L^-1 respectively. The In AUG0-T and In AUG0-∞ of the two for mulations were bioequivalent with analysis of variance and double single test, the relative bioavailability of guaiphenesin sustained release tablets was（107. 1 ± 8.0）%. CONCLUSION Guaiphenesin sustained release tablets had an effect of sustained release in Beagle dogs, and was bioequivalent to reference formulation.