盐酸伊曲康唑分散片在Beagle犬体内的药动学研究

 目的对盐酸伊曲康唑分散片在犬体内的药动学进行研究。方法将6条健康Beagle犬随机分为两组,采用单剂量双周期随机交叉实验设计,po110 mg的盐酸伊曲康唑分散片和100 mg伊曲康唑胶囊后,采用HPLC-荧光法测定犬血浆中伊曲康唑的浓度并计算ρ_max,t_max,AUC等参数,并以伊曲康唑胶囊(斯皮仁诺)为参比制剂进行生物等效性研究。对ρ_max,AUC进行双单侧t检验评价两制剂是否生物等效。结果试验制剂和参比制剂的ρ_max分别为(527.90±178.48)和(408.50±58.78)μg·L^-1;t_max分别为(2.58±0.66)和(2.67±1.51)h;AUC_0～48h分别为(4 511.96±1 691.94)和(3 326.72±1 633.60)μg·h·L^-1。结论盐酸伊曲康唑分散片的平均相对生物利用度为142.29%,较斯皮仁诺有明显提高(P<0.05),双单侧t检验的结果表明两制剂的lnAUC_0-48和ln ρ_max均为生物不等效。

Pharmacokinetics of itraconazole hydrochloride dispersible tablets in Beagle dogs

OBJECTIVE To study the pharmacokinetics of itraconazole hydrochloride dispersible tablets in Beagle dogs. METHODS According to a randomized two-period crossover design, the Beagle dogs were orally administered with 110 mg dispersible itraconazole hydrochloride tablets and 100 mg itraconazole capsules, respectively. Itraconazole in plasma was determined by HPLC-fluorescence, and the kinetic software was used to calculate the pharmacokinetic parameters.RESULTS ρ_max, t_max, AUC_0～48h of test dispersible tablets and reference capsules were(527.90±178.48), (408.50±58.78)μg·L^-1; (2.58 ± 0.66), (2.67 ± 1.51)h;(4 511.96±1 691.94), (3 326.72 ± 1,633.60)μg·h·L^-1,respectively.CONCLUSION The mean relative bioavailability is 142.29%.The AUC of the dispersible tablets are significantly higher than that of capsules(P<0.05) . The test and reference formulations are not bioequivalent.