Influence of Proteome Profiles and Intracellular Drug Exposure on Differences in CYP Activity in Donor-Matched Human Liver Microsomes and Hepatocytes
Christine Wegler, Pär Matsson, Veronica Krogstad, Jozef Urdzik, Hege Christensen, Tommy B. Andersson, Per Artursson
Abstract
for the five substrates. Nevertheless, scaling with CYP amounts improved the agreement in rank order for the majority of the substrates. Other factors, such as contribution of additional enzymes and variability in the proportions of active and inactive CYP enzymes in HLM and HH, may have to be considered to avoid the use of empirical scaling factors for prediction of drug metabolism.
Topics & Concepts
IntracellularMicrosomeCytochrome P450DrugPharmacologyChemistryDrug metabolismCYP2B6ProteomeBiochemistryBiologyIn vitroMetabolismCYP3A4Pharmacogenetics and Drug MetabolismDrug Transport and Resistance MechanismsMetabolism and Genetic Disorders