西罗莫司胶囊在人体内的生物等效性评价

Evaluation of Bioequivalence of Sirolimus Capsules in Healthy Chinese Male Volunteers

目的评价国产西罗莫司胶囊与市售西罗莫司口服液在中国健康男性体内的生物等效性。方法入选22名男性健康志愿者,随机交叉单剂量po西罗莫司胶囊或西罗莫司口服液5 mg,液质联用法测定全血中西罗莫司浓度。结果西罗莫司胶囊及口服液的药动学参数分别如下:ρmax分别为(26.62±9.97)和(25.28±5.98)ng.mL-1;tmax分别为(2.27±0.55)和(1.91±2.33)h;t1/2分别为(73.07±13.81)和(65.49±17.00)h;AUC0-t分别为(372.3±146.2)和(368.2±275.0)ng.h.mL-1,AUC0-∞分别为(466.8±194.3)和(442.3±324.4)ng.h.mL-1。相对生物利用度F0-t(112.4±34.61)%,F0-∞(117.2±39.93)%。经双单侧t检验确认,2种制剂的ρmax、AUC0-t及AUC0-∞均等效,非参数检验表明,试验药西罗莫司胶囊的tmax比参比口服溶液大,有显著性差异(P<0.05)。结论除tmax外,国产西罗莫司胶囊与市售西罗莫司口服液的ρmax和AUC0-t生物等效。

abstract OBJECTIVE To evaluate the bioequivalence of domestic sirolimus capsules and commercially available sirolimus oral solution in healthy Chinese volunteers.METHODS Twenty-two healthy Chinese male volunteers were enrolled and orally administered 5 mg sirolimus capsules or oral solution randomly.The concentrations of sirolimus in whole blood were determined by LC-MS/MS.RESULTS The pharmacokinetic parameters of sirolimus capsules and oral solution were as following： ρmax（26.62±9.97） and（25.28±5.98） ng· mL-1;tmax（2.27±0.55） and（1.91±2.33） h;t1/2（73.07±13.81） and（65.49±17.00） h;AUC0-t（372.3±146.2） and（368.2±275.0） ng·h·mL-1,AUC0-∞（466.8±194.3） and（442.3±324.4） ng·h·mL-1,respectively.The relative bioavailability F0-t was（112.4±34.61）% and F0-∞ was（117.2±39.93）%.Two-sided t-test of ρmax,AUC0-t and AUC0-∞ indicated that the preparations were equivalent,and non-parametric test showed that sirolimus capsules had larger tmax than the reference preparation with a significant difference（P0.05）.CONCLUSION The domestic sirolimus capsule is bioequivalent to the marketed sirolimus oral solution with significantly different tmax.