Authors
Eman El-Khateeb, Brahim Achour, Daniel Scotcher, Zubida M Al-Majdoub, Varinder Athwal, Jill Barber, Amin Rostami-Hodjegan
Publication date
2020/12/1
Journal
Drug Metabolism and Disposition
Volume
48
Issue
12
Pages
1271-1282
Publisher
American Society for Pharmacology and Experimental Therapeutics
Description
In vitro to in vivo extrapolation (IVIVE) enables prediction of in vivo clinical outcomes related to drug exposure in various populations from in vitro data. Prudent IVIVE requires scalars specific to the biologic characteristics of the system in each population. This study determined experimentally for the first time scalars in liver samples from patients with varying degrees of cirrhosis. Microsomal and cytosolic fractions were extracted from 13 noncirrhotic and 32 cirrhotic livers (six mild, 13 moderate, and 13 severe, based on Child-Pugh score). Fractional protein content was determined, and cytochrome P450 reductase activity was used to correct for microsomal protein loss. Although the median microsomal protein per gram liver (MPPGL) in mild, moderate, and severe cirrhosis (26.2, 32.4, and 30.8 mg⋅g−1, respectively) seemed lower than control livers (36.6 mg⋅g−1), differences were not statistically significant (Kruskal …
Total citations
20212022202320245464
Scholar articles
E El-Khateeb, B Achour, D Scotcher, ZM Al-Majdoub… - Drug Metabolism and Disposition, 2020