愈创甘油醚双层缓释片与普通片在犬体内药动学的比较研究

Pharmacokinetic Comparison between Guaifenesin Double-layer Extended Tablets and Common Tablets in Beagle Dogs

目的:比较愈创甘油醚双层缓释片与普通片在犬体內药动学特征。方法:Beagle犬单剂量给予600mg愈创甘油醚双层缓释片或愈创甘油醚普通片后,用RP-HPLC法测定犬血浆中愈创甘油醚的药物浓度,计算药动学参数和相对生物利用度。结果:Beagle犬单剂量口服给药后,受试制剂和参比制剂中愈创甘油醚的AUC_(0-12h)分别为(15.96±6.41)μg·h·ml^(-1)和(19.23±4.96)μg·h·ml^(-1);C_(max)分别为(7.31±2.86)μg·ml^(-1)和(14.24±5.34)μg·ml^(-1);t_(max)分别为(0.79±0.25)h和(1.08±0.38)h;t_(1/2)分别为(2.50±1.67)h和(0.42±0.05)h;MRT_(0-1)分别为(2.37±0.61)h和(1.42±0.30)h。结论:愈创甘油醚双层缓释片的C_(max)较普通片显著降低,MRT_(0-1)和t_(1/2)明显延长,差异有统计学意义(P<0.05),说明该受试制剂具备一定的缓释药动学特征。

Objective ： To compare the pharmacokinetics of guaifenesin double-layer extended tablets and common tablets in Beagle dogs. Method： Each dog was randomly given a single oral dose of 600 mg guaifenesin double-layer extended tablets or common tab- lets. Plasma samples were obtained and a RP-HPLC method was applied to determine guaifenesin in the plasma samples. Result： After oral administration of guaifenesin double-layer extended tablets or common tablets, the major pharmacokinetic parameters were as fol- lows： AUC0-12h were （15.96±6.41） μg · h · ml-1 and （19.23 ±4.96） μg · h · ml-1;Cmaxwere （7.31 ±2.86） μg · ml^-1 and （ 14.24 ± 5.34） μg · ml^-1 ; t1/2 were （0.79 ± 0.25 ） h and （ 1.08 ± 0.38 ） h ; tj/2 were （ 2.50 ±1. 67 ） h and （0.42 ± 0.05 ） h ; MRT0-4 were （2.37 ± 0.61 ） h and （ 1.42 ± 0.30） h. Conclusion： There are significantly statistical differences between the two kinds of tablets in Can, MRT0-4 and t1/2（P 〈 0.05）. Compared with that of the common tablets, Cmax of the extended tablets is significantly lower; MRT0-4 and t1/2 are both much longer. These data show that the double-layer extended tablets exhibit the delayed release property.