Role of NADPH-cytochrome P450 reductase and cytochrome-b5/NADH-b5 reductase in variability of CYP3A activity in human liver microsomes |
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| Authors: | L Gan LL von Moltke LA Trepanier JS Harmatz DJ Greenblatt MH Court |
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| Affiliation: | Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, Massachusetts 02111, USA. |
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| Abstract: | 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 (
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