Characterizing the Effects of Race/Ethnicity on Acetaminophen Pharmacokinetics Using Physiologically Based Pharmacokinetic Modeling

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• 作者：Todd J. Zurlinden…
• 刊名：European Journal of Drug Metabolism and Pharmacokinetics
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：42
• 期：1
• 页码：143-153
• 全文大小：
• 刊物主题：Pharmacology/Toxicology; Pharmacy; Human Physiology; Pharmaceutical Sciences/Technology; Medical Biochemistry;
• 出版者：Springer International Publishing
• ISSN：2107-0180
• 卷排序：42

文摘

Background and ObjectivesAcetaminophen (APAP, paracetamol) is currently the principal cause of acute liver failure in both the USA and the UK. However, relatively little is known about the influence of genes and race/ethnicity on the disposition of APAP and the extent to which genetic variation and ethnicity may predispose individuals to a higher risk of APAP-induced hepatotoxicity. The objective of this research was to develop subpopulation-specific physiologically based pharmacokinetic (PBPK) models for two genetically different groups (Western Europeans and East Asians) and then use the models to quantify the difference in absorption, distribution, metabolism, and excretion (ADME) of APAP between these groups.