Improved Determination of Drug Metabolism by Perifusion of Recombinant V79 Cells Carrying Human CYP3A4

Recombinant V79Mz cell lines stably co-expressing human CYP3A4 and human NADPH-cytochrome P450 oxidoreductase were used to compare testosterone metabolism under conventional stationary cultivation and under perifusion. In contrast to stationary culture, steady-state conditions for the production of...

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Bibliographic Details
Published in:Toxicology in vitro 1999-08, Vol.13 (4), p.639-643
Main Authors: Gebhardt, R, Lippert, C, Schneider, A, Doehmer, J
Format: Article
Language:English
Subjects:
Biological and medical sciences
cytochrome P450
cytochrome P4503A4
drug metabolism
General pharmacology
Medical sciences
perifusion
Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions
Pharmacology. Drug treatments
recombinant cell lines
testosterone
V79 cells
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Summary:Recombinant V79Mz cell lines stably co-expressing human CYP3A4 and human NADPH-cytochrome P450 oxidoreductase were used to compare testosterone metabolism under conventional stationary cultivation and under perifusion. In contrast to stationary culture, steady-state conditions for the production of 6 β-hydoxytestosterone were established in the perifusion system even when different concentrations of testosterone were infused sequentially. As a consequence of these favourable conditions, threefold higher maximal metabolic rates could be measured and kinetic constants could be determined more reproducibly than in stationary culture. The results indicate that CYP3A4 shows an autocatalytic reaction kinetic probably due to two binding sites for testosterone.
ISSN:0887-2333
1879-3177
DOI:10.1016/S0887-2333(99)00020-X