Zhu C J, Li Z J, Leng W
Hormones Laboratory, National Institute for the Control of Pharmaceutical and Biological Products, Beijing, China.
Zhongguo Yao Li Xue Bao. 1997 Nov;18(6):489-93.
To develop a method for measurement of biological activity of recombinant DNA-derived somatotropin (rhGH).
The effects of varying the route, frequency and period of administration of GH, the sex of test animals on the biological responses, body weight gain (BWG), and tibial epiphyseal width (TEW), of hypophysectomized (Hypox) rats were compared, respectively. 4-d BWG, 6-d BWG, and 6-d TEW tests were carried out simultaneously in the same group of Hypox rats to determine the biopotency of GH preparations according to a parallel line bioassay (6-point assay). The final result was chosen from the test which had smaller values for the index of precision (lambda) and the average rate of fiducial limits (ARFL) than other tests.
No significant differences in the responses between male and female rats, between sc and im, once daily and twice daily injections of bGH were found. But the BWG and TEW of Hypox rats injected with 0.045 and 0.135 IU.d-1 of bGH for 6 d were significantly greater than that for 4 d. Both 4-d BWG test and 6-d BWG test in the range from 0.020 to 0.500 IU.d-1 had values for lambda = 0.0660 and 0.1747, and for r = 0.9000 and 0.9237, respectively. Three estimates of rhGH preparation compared with the International Standard for somatotropin (IShGH), 4.6132, 3.9829, and 4.8023 IU/ampoule, were obtained separately from 4-d BWG test, 6-d BWG test and 6-d TEW test. And the result from 6-d BWG test was reported finally because it had smaller values for lambda and ARFL (0.0608 and 37.907%) than other two tests.
Both BWG test and TEW test can be carried out simultaneously in the same group of Hypox rats. 6-d BWG test seemed to be more suitable for potency determination of GH preparations than 4-d BWG test and 6-d TEW test.
建立一种测量重组DNA来源的生长激素（rhGH）生物活性的方法。
分别比较生长激素给药途径、频率和周期的变化，以及受试动物性别对垂体切除（Hypox）大鼠生物反应、体重增加（BWG）和胫骨骨骺宽度（TEW）的影响。在同一组Hypox大鼠中同时进行4天BWG、6天BWG和6天TEW试验，根据平行线生物测定法（6点测定法）确定生长激素制剂的生物效价。最终结果从精密度指数（λ）和可信限平均率（ARFL）值比其他试验小的试验中选取。
未发现雄性和雌性大鼠之间、皮下注射和肌肉注射之间、每日一次和每日两次注射bGH之间的反应有显著差异。但是，注射0.045和0.135IU·d-1的bGH 6天的Hypox大鼠的BWG和TEW显著大于注射4天的大鼠。在0.020至0.500IU·d-1范围内，4天BWG试验和6天BWG试验的λ值分别为0.0660和0.1747，r值分别为0.9000和0.9237。从4天BWG试验、6天BWG试验和6天TEW试验中分别获得了与生长激素国际标准品（IShGH）相比的rhGH制剂的三个效价估计值，分别为4.6132、3.9829和4.8023IU/安瓿。最终报告的是6天BWG试验的结果，因为它的λ和ARFL值（0.0608和37.907%）比其他两个试验小。
BWG试验和TEW试验可在同一组Hypox大鼠中同时进行。6天BWG试验似乎比4天BWG试验和6天TEW试验更适合于生长激素制剂的效价测定。
