高效复合干扰素人体药动学及生物等效性的研究

STUDY ON PHARMACOKINETICS AND BIOEQUIVALENCE OF RSIFN-CO IN HEALTHY VOLUNTEERS

[目的]以美国安进公司生产的干复津注射液(Infergen)为参比制剂,对四川辉阳生命工程股份有限公司研制的冻干重组高效复合干扰素粉针剂(rSIFN-co)人体药动学和生物等效性进行比较研究。[方法]对18名健康男性志愿受试者采用随机双交叉自身对照试验,受试者分别单剂皮下注射试验制剂9μg和参比制剂9μg后,用放射免疫法测定干扰素诱生的2′,5′-寡腺苷酸合成酶(2′5′-OAS)浓度,由DASver1.0程序计算药代动力学参数并进行生物等效性分析。[结果]试验制剂rSIFN-co9μg与参比制剂Infergen9μg的AUC0-48分别为(4184.1±1938.7)pmol·h/dL及(3336.8±1365.5)pmol·h/dL,Cmax分别为(204.42±100.16)pmol·dL-1及(271.77±150.53)pmol·dL-1,Tmax分别为(23.00±1.03)h及(23.22±1.0)h。参比制剂和试验制剂Tmax的差异无统计学意义(P=0.163),Cmax和AUC0-48差异有统计学意义(P=0.031,P=0.014),其相对生物利用度为125.4%。[结论]两制剂生物等效。冻干重组高效复合干扰素粉针剂(rSIFN-co)具有临床推广价值。

[Objective] To study the pharmacokinetics and bioequivalence of Lyophilized Recombinant Super Compound Interferon （rSIFN-co）. [Methods] A single subcutaneous injection dose of rSIFN-co from either 9μg test injection or its 9μg reference injection Infergen was given to 18 healthy male volurtteers by a randomized cross-over design. The concentration in plasma of 2＇5＇-OAS, a active metabolity of interferon, was determined by radioimmunoassay （RIA） method. The pharmaclokinetics and bioequivalence of the test injection were compared with the reference injection. [Results] The main pharmacokinetics parameters of test injection and reference injection were as follow： AUC0-48 were 4184.1 ±1938.7pmol·h/dL and 3336.8±1365.5 pmol·h/dL respectively, Cmax were 204.42±100.16 pmul·dL^-1 and 271.77±150.53 prnol·dL^-1 respectively, rTmax were 23.00±1.03 h and 23.22±1.0 h respectively. Through the one two-sided test and the analysis of covariance, no significant difference between the Tmax of the two formulations was found （P = 0.163）. However, the Cmax, and AUC0-48 of the test rSIFN,co was higher than that of reference Infergen （P = 0.031, P = 0.014）. The relative bioavallability of the test rSIFN-co was 125.4% of the reference injection. [Conclusion] The two formulations are bioequivalent, the injectable powder of rSIFN-co has clinical popularization value.