Zhang Xueyan, Zhou Baisong, Gong Yihan, Liu Yulin
Department of Recombinant Protein Drug, Changchun Institute of Biological Products, Changchun, 130012, China.
Sci Rep. 2025 May 7;15(1):15932. doi: 10.1038/s41598-025-98813-3.
Recombinant human interferon Alfa-2b vaginal suppository is a gynecological preparation mainly made of interferon, commonly used to treat diseases related to viral infections such as cervical erosion. As a recombinant protein drug, it is important to pay attention to the possibility of modifications that may lower the quality of the drug during the production process. The aim of this study is to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of this product in Chinese rhesus macaque after purification process changes, and to demonstrate that there is no difference in the biological activity of recombinant human interferon Alfa-2b vaginal suppository stock solution before and after process changes. There are 12 test animals: Chinese rhesus macaques who received a two-group crossover design and were subcutaneously injected with the same active dose of 500,000 IU/kg around the navel in the abdomen. According to maximum concentration (C) and time of maximum concentration (T) within non-parametric test (P > 0.05), geometric mean ratio of PK parameter C for the drugs after purification process changes (sample S) compared to the before purification process changes one (sample R) was 97.09%, with a 90% confidence interval (CI) of 87.39-107.87%. The geometric mean ratio C of serum Beta2-microglobulin (PD) for PD index is 100.07%, with a 90% CI of 97.16-103.07%; Geometric mean ratio of AUEC is 98.91%, with a 90% CI of 96.53-101.34%. The geometric mean of the PD index, neopterin PD, is 97.75%, with a 90% CI of 92.53-103.25%; Geometric mean of AUEC is 105.59%, with a 90% CI ranging from 97.22 to 114.68%. The important parameters of PK/PD meet the equivalence requirements, and biological activity of the recombinant human interferon Alfa-2b vaginal suppository stock solution after purification process change is no different from before the change. Under the same active dose administration conditions, the same biological effects were produced, achieving the same effect as before the change.
重组人干扰素α-2b阴道栓是一种主要由干扰素制成的妇科制剂，常用于治疗与病毒感染相关的疾病，如宫颈糜烂。作为一种重组蛋白药物，在生产过程中关注可能降低药物质量的修饰可能性很重要。本研究的目的是评估纯化工艺改变后该产品在中国恒河猴体内的药代动力学（PK）和药效学（PD）特征，并证明重组人干扰素α-2b阴道栓原液在工艺改变前后的生物活性无差异。有12只试验动物：接受两组交叉设计的中国恒河猴，在腹部脐周皮下注射相同活性剂量500,000 IU/kg。根据非参数检验中的最大浓度（C）和最大浓度出现时间（T）（P＞0.05），纯化工艺改变后药物（样品S）与纯化工艺改变前药物（样品R）的PK参数C的几何平均比值为97.09%，90%置信区间（CI）为87.39 - 107.87%。PD指标血清β2-微球蛋白（PD）的几何平均比值C为100.07%，90% CI为97.16 - 103.07%；AUEC的几何平均比值为98.91%，90% CI为96.53 - 101.34%。PD指标新蝶呤PD的几何平均值为97.75%，90% CI为92.53 - 103.25%；AUEC的几何平均值为105.59%，90% CI为97.22至114.68%。PK/PD的重要参数符合等效性要求，纯化工艺改变后重组人干扰素α-2b阴道栓原液的生物活性与改变前无差异。在相同活性剂量给药条件下，产生了相同的生物学效应，达到了与改变前相同的效果。
