Evaluating gender effect in the generic bioequivalence studies by physiologically based pharmacokinetic modeling – A case study of dextromethorphan modified release tablets

Author:

Gundeti Manoj1,Murthy Aditya2ORCID,Jamdade Shubham1,Ahmed Tausif3ORCID

Affiliation:

1. Global Clinical Management, IPDO, Dr Reddy’s Laboratories Ltd Hyderabad India

2. Biopharmaceutics Group, Global Clinical Management, IPDO, Dr Reddy’s Laboratories Ltd Hyderabad India

3. Department of Biopharmaceutics and Bioequivalence, Global Clinical Management, IPDO Dr Reddy’s Laboratories Ltd Hyderabad India

Abstract

AbstractThe United States Food and Drug Administration guidelines for the bioequivalence (BE) testing of the generic drug products suggests that there should be an equal proportion of male and female population in the BE study. Despite this requirement, many generic drug companies do not maintain the suggested proportion of female population in their studies. Several socio‐economic and cultural factors lead to lower participation of the females in the BE studies. More recently, the regulatory agencies across the globe are requesting the generic drug companies to demonstrate the performance of their drug products in the under‐represented sex via additional studies. In this work, we describe the case of Dextromethorphan modified release tablets where the gender effect on the product performance was evaluated by physiologically based pharmacokinetic (PBPK) modeling approach. We have compared the drug product's performance by population simulations considering four different scenarios. The data from all‐male population (from in house Pharmacokinetic [PK] BE studies) was considered as a reference and other scenarios were compared against the all‐male population data. In the first scenario, we made a comparison between all‐male (100% male) vs all‐female (100% female) population. Second scenario was as per agency’s requirements—equal proportion of male and female in the BE study. As an extreme scenario, 100% male vs 30:70 male:female was considered (higher females than males in the BE studies). Finally, as a more realistic scenario, 100% male versus 70:30 male:female was considered (lower females than males in the BE studies). Population PK followed by virtual BE was employed to demonstrate the similarity/differences in the drug product performance between the sexes. This approach can be potentially utilized to seek BE study waivers thus saving cost and accelerating the entry of the generic products to the market.

Publisher

Wiley

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3