重组人生长激素在健康猕猴体内的比较药代动力学

摘要

Objective; To investigate the pharmacokinetics of two recombinant human growth hormone ( rh-GH) injections produced by different domestic companies in healthy rhesus monkeys for evaluation of similarity. Methods; A self-controlled crossover design was used. Eight rhesus monkeys were administered a single dose of test or reference rhGH via subcutaneous injection at 0. 35 IU· kg-1 . The concentration of rhGH in serum was measured by an enzyme linked immunosorbent assay (ELISA) method. Pharmacokinetic parameters were calculated by statistical moment method. The pharmacokinetic parameters were evaluated by 3P97 software referring to the standard of bioequivalence. Results; The specificity, sensitivity, precision and accuracy of the present ELISA method met the requirements of pharmacokinetic study. The concentration-time profile of the test rhGH was well comparable with that of the reference rhGH. The key pharmacokinetic parameters of the test and reference products were as follows; AUC0.12h was (512 ±102) and (476 ±71) μg·h·L-1; AUC0-∞ was (538 ±115) and (494 ±77) μg-h·L-1; Cmax was (108 ±18) and (96 ±23) n·g·L-1; t1/2 was (2.8 ±0.7) and (2.2 ±0.7) h; MRT was (4.2 ±0.8) and (4.0 ±0.8) h; CLs/Fsc was (0.047 ±0.014) and (0.060 ±0.013) L·lh-1·kg-1; V,/Ftc was (0.194 ±0.04) and (0.24 ±0.06) L·kg , respectively. When compared to the reference rhGH, the 90% confidence intervals of the bioavailability of the test rhGH evaluated by AUC0-12h, AUC0-∞ and Cmax were 89.2% -114.3% , 87.4% -112.7% and 98. 5% ~ 124.4% , respectively. The relative bioavailability of the test rhGH was ( 109 ±15)% when e-valuated by AUC0-∞. . Conclusion: The pharmacokinelic parameters of the test and reference rhGH meet the bioequiv-alence acceptance criteria. These two rhGH products showed similar pharmacokinetic characters in rhesus monkeys.%目的:比较两种国产重组人生长激素在健康猕猴体内的药代动力学,评价两种药物的相似性.方法:采用交叉自身比较设计,8只健康成年猕猴分别单次皮下注射受试品和参比品0.35 IU· kg-1；采用酶联免疫吸附分析法检测血清中药物浓度,统计矩方法计算各主要药代动力学参数；采用3P97软件参考生物等效性标准对参数进行评价.结果:方法的特异性、灵敏度、精密度和准确度均符合药代动力学研究要求.受试品与参比品的血药浓度-时间曲线基本一致,主要药代动力学参数AUC0～12h分别为(512±102)和( 476±71) μg·h·L-1；AUC0～∞分别为(538 ±115)和(494±77) μg·h·L-1；Cmax分别为(108 ±18)和(96±23)μg·L-1；t1/2分别为(2.8±0.7)和(2.2±0.7) h;MRT分别为(4.2±0.8)和(4.0±0.8)h; CLs/Fsc分别为(0.047 ±0.014)和(0.060 ±0.013) L·h-1·kg-1；Vd/Fsc分别为(0.194±0.04)和(0.24 ±0.06) L·kg-1.以AUC0～∞计算,受试品与参比品比较,相对生物利用度F为(109±15)％.受试品相对于参比品的生物等效性用AUC0～12 h,AUC0～∞和Cmax的90％可信区间评价分别为89.2％～114.3％,87.4％～112.7％和98.5％～124.4％,均符合生物等效性判断标准.结论:受试品与参比品药代动力学参数评价结果满足生物等效接受标准；两种重组人生长激素在猕猴体内呈现相同的药代动力学特征.