关键词: 伊曲康唑, 生物等效性, HPLC-MS/MS

Abstract: AIM: To study the bioequivalence of domestic Itraconazole capsules in healthy Chinese volunteers before diet or after diet respectively.METHODS: There were two randomized, open-label, two-period clinical studies, and 24 healthy Chinese male volunteers were enrolled in each study.All the volunteers in each study had taken a single dose of 200 mg Itraconazole test capsules and 200 mg of its reference. The plasma Itraconazole concentration were determined by HPLC-MS/MS. The major harmacokinetic parameters were calculated, the bioequivalence of Itraconazole test capsule and its reference before diet as well as after diet were evaluated respectively.RESULTS: The pharmacokinetic parameters before diet were as follows: C_max were (124±79) and (124±86) μg/L;t_max were (2.9±0.8) and (2.5±0.9) h;AUC_0-t were(1320±826) and (1348±1095) μg·h·L^-1;AUC_0-∞ were (1420±902)and(1444±1148) μg·h·L^-1;AUC_0-t/AUC_0-∞ were (93.0±4.9)% and (92.3±5.1)%;t_1/2 were (17.7±4.7) and (18.1±2.8) h. The relative bioavailability of the test capsule was (106.5±35.4)%.The pharmacokinetic parameters after diet were as follows: C_max were (202±107) and (218±109) μg/L;t_max were(4.2±0.8)and (3.9±0.8) h;AUC_0-t were(2494±1163)and(2657±1424)μg·h·L^-1;AUC_0-∞ were (2705±1290) and (2870±1578) μg·h·L^-1;AUC_0-t/AUC_0-∞ were (92.3±5.2)%/(93.6±4.1)%;t_1/2 were (19.3±5.5) and (18.0±5.1) h. The relative bioavailability of the test capsule was (100.5±33.1) %.CONCLUSION: The Itraconazole test capsule and its reference were bioequivalent both when administrated before diet and after diet.The C_max and AUC were both significant higher when administrated after diet, so it is better to dose after diet for Itraconazole capsule in order to gain a higher bioavailability and an increased effect.

Key words: Itraconazole, Bioequivalence, HPLC-MS/MS