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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。
Objective To evaluate the bioequivalence of domestic sirolimus capsules and commercial sirolimus oral solution in healthy Chinese men. Methods A total of 22 healthy volunteers were enrolled in this study. A single crossover dose of sirolimus capsule or sirolimus oral solution 5 mg was used. The concentration of sirolimus in whole blood was determined by LC / MS. Results The pharmacokinetic parameters of sirolimus capsule and oral solution were as follows: ρmax were (26.62 ± 9.97) and (25.28 ± 5.98) ng.mL-1, respectively; tmax was (2.27 ± 0.55) and (1.91 ± 2.33 (h); t1 / 2 were (73.07 ± 13.81) and (65.49 ± 17.00) h respectively; AUC0-t was (372.3 ± 146.2) and (368.2 ± 275.0) ng.h.mL- (466.8 ± 194.3) and (442.3 ± 324.4) ng.h.mL-1. Relative bioavailability F0-t (112.4 ± 34.61)%, F0-∞ (117.2 ± 39.93)%. The two-sided t-test confirmed that the two formulations of ρmax, AUC0-t and AUC0-∞ are equivalent, non-parametric tests showed that the test drug sirolimus capsule tmax greater than the reference oral solution, a significant difference ( P <0.05). Conclusion In addition to tmax, the domestic sirolimus capsules and commercial sirolimus oral pmax and AUC0-t bioequivalent.