盐酸伊曲康唑分散片在Beagle犬体内的药动学研究

Pharmacokinetics of itraconazole hydrochloride dispersible tablets in Beagle dogs

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,po 110 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ρmax,tmax,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ρmax,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ρmax分别为(527.90±178.48)和(408.50±58.78)μg·L-1;tmax分别为(2.58±0.66)和(2.67±1.51)h;AUC0～48 h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lnAUC0-48和ln ρmax均为生物不等效。

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 103 mg itraconazole capsules, respectively, Itraconazole in plasma was determined by HPLC-fluorescence, and the kinetic software was used to calculate the pharmacokinetic parameters, RESULTS ρmax, tmax, AUG0～48h 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.