Role of NADPH-Cytochrome P450 Reductase and Cytochrome-b5/ NADH-b5 Reductase in Variability of CYP3A Activity in Human Liver Microsomes

NADPH-cytochrome P450 reductase (CPR) and cytochrome-b(5) (b(5)) together with NADH-b(5) reductase (b(5)R) play important roles in cytochrome P450 3A-mediated drug metabolism via electron transfer. However, it is not clear whether variability in expression of these accessory proteins contributes to...

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Veröffentlicht in:	Drug metabolism and disposition 2009-01, Vol.37 (1), p.90-96
Hauptverfasser:	LU GAN, VON MOLTKE, Lisa L, TREPANIER, Lauren A, HARMATZ, Jerold S, GREENBLATT, David J, COURT, Michael H
Format:	Artikel
Sprache:	eng
Schlagworte:	Aging - metabolism Biological and medical sciences Cytochrome P-450 CYP3A Cytochrome P-450 Enzyme System - metabolism Cytochrome-B Reductase - antagonists & inhibitors Cytochrome-B Reductase - metabolism Enzyme Inhibitors - pharmacology Female Humans Male Medical sciences Microsomes, Liver - enzymology NADPH-Ferrihemoprotein Reductase - antagonists & inhibitors NADPH-Ferrihemoprotein Reductase - metabolism Pharmacology. Drug treatments Sex Factors Thioctic Acid - pharmacology
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Zusammenfassung:	NADPH-cytochrome P450 reductase (CPR) and cytochrome-b(5) (b(5)) together with NADH-b(5) reductase (b(5)R) play important roles in cytochrome P450 3A-mediated drug metabolism via electron transfer. However, it is not clear whether variability in expression of these accessory proteins contributes to the known interindividual variability in CYP3A activity. CPR and b(5) were measured in human liver microsomes (HLMs) by spectrophotometry and immunoblotting. HLMs from elderly (>or=46 years) male donors (n=11) averaged 27% (P=0.034) and 41% (P=0.011) lower CPR levels than young (
ISSN:	0090-9556 1521-009X
DOI:	10.1124/dmd.108.023424