基于胃肠道生理模型的口服药物吸收预测

中国临床药理学与治疗学 ›› 2010, Vol. 15 ›› Issue (6): 656-662.

基于胃肠道生理模型的口服药物吸收预测

黎国富^1,2, 杨劲¹, 张雪莹¹, 赵浩如¹

¹中国药科大学药物代谢与药物动力学研究中心, ²中药制剂教研室,南京 210009,江苏

收稿日期:2010-02-26 修回日期:2010-06-06 出版日期:2010-06-26 发布日期:2020-09-16
通讯作者: 杨劲,男,副教授,研究方向:药物代谢动力学和生物统计学。 Tel: 025-83271386 E-mail:yangjingqw@263.net
赵浩如,男,教授,研究方向:中药制剂新技术。 Tel: 025-83201966 E-mail:zhaohaoruchina@yahoo.com.cn
作者简介:黎国富,男,硕士研究生,研究方向:药物代谢动力学与生物药剂学。Tel: 025-83271386 E-mail: lihs454@gmail.com

Physiologically based gastrointestinal models for the prediction of oral drug absorption

LI Guo-fu^1,2, YANG Jin¹, ZHANG Xue-ying¹, ZHAO Hao-ru²

¹ Key Lab of Drug Metabolism and Pharmacokinetics, ² Department of Pharmaceutics of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing 210009, Jiangsu, China

Received:2010-02-26 Revised:2010-06-06 Online:2010-06-26 Published:2020-09-16

摘要/Abstract

摘要： 药物的口服吸收受到许多生理因素的影响,如胃肠液成分、pH、肠道内传输、转运和代谢等。在进行非临床和临床体内试验之前,如果仅仅依靠体外数据能够准确地预测药物的口服吸收,将会大大提高新药研发的效率。在深入理解口服吸收过程的基础上发展起来的胃肠道生理模型为从事新药研发的科研工作者提供了这种机会。这些生理模型可以与经典的药动学模型紧密衔接,用于预测药物的口服吸收速度和程度。本文综述了胃肠道生理模型的最新进展,并对不同的模型进行了比较和讨论。

关键词: 胃肠道生理模型, 生理药动学模型, 高级房室吸收和传输(ACAT)模型, 高级溶出、吸收和代谢(ADAM)模型, 生物药剂学分类系统

Abstract: Oral drug absorption is influenced by different physiological factors, such as composition of gastrointestinal fluid, pH, transit, transport and metabolism. The ability to accurately predict the oral drug absorption only depended on in vitro results, before preclinical or clinical researches will improve the efficient of drug development. Various physiologically based gastrointestinal models based on the profound understanding of oral absorption process provide an opportunity to assess in vivo oral absorption. These physiological models can link to classical pharmacokinetic models to predict the rate and extent of oral drug absorption. This paper reviews the principle and new application of these physiological models, then compare and discuss with those.

Key words: Physiologically based gastrointestinal models, Physiologically-based pharmacokinetic (PBPK) models, Advanced compartmental absorption and transit (ACAT) model, Advanced dissolution absorption, and metabolism (ADAM) model, Biopharmaceutics classification system

中图分类号:

R969.1

黎国富, 杨劲, 张雪莹, 赵浩如. 基于胃肠道生理模型的口服药物吸收预测[J]. 中国临床药理学与治疗学, 2010, 15(6): 656-662.

LI Guo-fu, YANG Jin, ZHANG Xue-ying, ZHAO Hao-ru. Physiologically based gastrointestinal models for the prediction of oral drug absorption[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(6): 656-662.

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