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Drug Metabolism and Disposition Fast Forward
First published on June 28, 2007; DOI: 10.1124/dmd.107.015743

0090-9556/07/3510-1733-1736$20.00
DMD 35:1733-1736, 2007

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Disparity in Holoprotein/Apoprotein Ratios of Different Standards Used for Immunoquantification of Hepatic Cytochrome P450 Enzymes

H. F. Perrett, Z. E. Barter, B. C. Jones, H. Yamazaki, G. T. Tucker, and A. Rostami-Hodjegan

Academic Unit of Clinical Pharmacology, University of Sheffield, Royal Hallamshire Hospital, Sheffield, United Kingdom (H.F.P., Z.E.B., G.T.T., A.R.-H.); Simcyp Ltd., Sheffield, United Kingdom (Z.E.B., G.T.T., A.R.-H.); Department of Pharmacokinetics, Dynamics and Metabolism, Pfizer Global Research and Development, Sandwich, Kent, United Kingdom (B.C.J.); and Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Machida, Tokyo, Japan (H.Y.)

An analysis of reported hepatic abundances of CYP3A4 and 3A5 indicated that values determined by immunoquantification using commercially available, unpurified recombinant enzymes as standards are significantly lower than those determined using purified enzymes or human liver microsomes characterized with lysosomal peptides (CYP3A4: mean 45 versus 121 pmol/mg protein, p < 0.01; CYP3A5: mean 28 versus 83 pmol/mg protein, p < 0.05). When immunoquantifying cytochromes P450 (P450s), it is assumed that the holoprotein (holo)/apoprotein ratio is the same in the samples and the standard. Estimates of holo/apoprotein ratios from data reported for a range of P450s purified from human liver and non-commercial recombinant systems indicated less than complete and variable heme coupling dependent on enzyme and system.

Address correspondence to: Dr. Zoe Barter, Floor M, The Royal Hallamshire Hospital, Sheffield S10 2JF, U.K. E-mail: z.barter{at}sheffield.ac.uk




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