国产与进口熊去氧胆酸胶囊在健康人体的生物等效性

Bioequivalence of domestic and imported ursodeoxycholic acid capsules in healthy volunteers

目的以进口熊去氧胆酸胶囊(抗胆石症药)为参比制剂,评价国产熊去氧胆酸胶囊的生物等效性。方法 21名男性健康受试者采用随机、自身交叉前后对照试验方案,用液相色谱-质谱联用法,以盐酸西替利嗪为内标,测定血浆中熊去氧胆酸的浓度,评价试验制剂的相对生物利用度。结果单剂量口服熊去氧胆酸胶囊试验制剂和参比制剂各500 mg后的AUC0-24h分别为(18.9±7.0)和(19.0±5.5)mg·h·L-1;AUC0-∞分别为(22.6±11.8)和(20.9±5.9)mg·h·L-1;tm ax分别为(2.4±0.4)和(2.3±0.6)h;Cmax分别为(9.2±5.0)和(8.2±4.0)mg·L-1。试验制剂的F0-24h为(104±38)%。对AUC0-24h、AUC0-∞、Cmax和tmax作方差分析、双单侧t检验及非参数法秩和检验,结果2组间无统计学差异。结论试验制剂与参比制剂具有生物等效性。

Objective To evaluate the bioequivalence of ursodexycholic acid capsules improved by a company comparing with the reference produced by Dr. Falk Pharma GmbH. Methods 21 healthy male volunteers were randomly administered with an oral single crossover dose of test. The concentrations of ursodexycholic acid in plasma were determined by LC -MS using cetirizine hydrochloride as internal standard. Results The AUC0-24h were （18.9 ±7.0）and （19.0 ±5.5） mg·h·L^-1; AUC0-∞ were （22.6 ± 11.8 ） and （20. 9 ±5.9 ） mg·h·L^-1 ; tmax were （2.4±0.4） and （2.3 ±0.6）h; Cmax were（9.2 ±5,0） and （8.2 ±4. 0）mg·L^-1, respectively for test and reference after an oral single dose of 500 mg ursodexycholic acid capsules. There were no significant difference between the main pharmacokinetic parameters and the relative bioavailability of the test was （ 104. 4 ±38.3） %. Conclusion It is bio- equivalent for the test capsules comparing with the reference capsules after a single oral dose of 500 mg ursodexycholic acid capsules.