平行人工膜渗透模型在枸橼酸西地那非片过评仿制药生物等效性预测中的应用  

The Application of Parallel Artificial Membrane Permeability Model in Predicting Bioequivalence of Generic Sildenafil Citrate Tablets Passed the Consistency Evaluation

作　　者：张树栋 吴斌 吴兆伟 张喆 王琳 ZHANG Shudong;WU Bin;WU Zhaowei;ZHANG Zhe;WANG Lin(Beijing Institute for Drug Control,NMPA Key Laboratory for Research and Evaluation of Generic Drugs,Beijing Key Laboratory of Analysis and Evaluation on Chinese Medicine,Beijing 102206,China)

机构地区：[1]北京市药品检验研究院,国家药品监督管理局仿制药研究与评价重点实验室,中药成分分析与生物评价北京市重点实验室,北京102206

出　　处：《中国医药导刊》2025年第3期314-320,共7页Chinese Journal of Medicinal Guide

基　　金：北京市药品监督管理局药品监管科学行动计划(第一批)项目。

摘　　要：目的:采用平行人工膜渗透模型,对两家已经通过仿制药一致性评价的枸橼酸西地那非片的渗透速率进行研究,预测其人体生物等效性,为该品种过评后的监管提供可行方案。方法:采用Macro FluxTM型药物溶出度与渗透速率测试系统,建立了基于平行人工膜渗透性的枸橼酸西地那非片体外溶出-渗透模型,分别测定两家过评企业产品在模拟空腹介质中的溶出行为和渗透速率,并同参比制剂进行比较,预测其人体生物等效性。结果:两家过评企业的渗透速率和累积渗透量分别为(1.3187±0.0198)μg·min^(-1)·cm^(-2)、(1.3416±0.0071)μg·min^(-1)·cm^(-2)和(392.2666±8.2958)μg、(399.0267±15.4297)μg。经模型预测两家过评企业制剂与参比制剂生物等效。结论:该模型能更准确地预测评估枸橼酸西地那非片在胃肠道的吸收行为及临床疗效,为药物有效性评价提供新工具。该研究为已通过一致性评价的仿制药的监管提供科学的评价方法及监测工具,支撑药品全生命周期的科学监管。Objective:To study the permeation rate of sildenafil citrate tablets from two companies that have passed the generic drug consistency evaluation,by using a parallel artificial permeability model,and to predict the human bioequivalence of these two compa⁃nies'products compared to the reference formulation,and providing a feasible regulatory approach for the post-evaluation supervision of this product.Methods:Using the Macro FluxTM drug dissolution and permeation rate testing system,an in vitro dissolution and perme⁃ation model of sildenafil citrate tablets based on parallel artificial membrane permeability was established.The dissolution behavior and permeation rate of two companies passed the consistency evaluation in simulated fasting medium were determined and compared with the reference formulation to predict their human bioequivalence.Results:The permeation rate of the preparations that passed the consis⁃tency evaluation were(1.3187±0.0198)μg·min^(-1)·cm^(-2),(1.3416±0.0071)μg·min^(-1)·cm^(-2),and the cumulative permeation were(392.2666±8.2958)μg,(399.0267±15.4297)μg.The model predicted that the formulations from the two evaluated companies are bioequivalent to the reference formulation.Conclusion:This model can more accurately predict and assess the absorption behavior and clinical efficacy of sildenafil citrate tablets in the gastrointestinal tract,providing a new strategy for the efficacy evaluation of this drug.This study offers a scientific evaluation method and monitoring tools for the regulation of generic drugs that have passed the consistency evaluation,supporting the scientific supervision of the entire lifecycle of pharmaceuticals.

关 键 词：枸橼酸西地那非片 平行人工膜渗透模型 生物等效性 仿制药 一致性评价 

分 类 号：R945[医药卫生—微生物与生化药学]