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Xenobiotica
the fate of foreign compounds in biological systems
Volume 24, 1994 - Issue 3
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Original Article

7-Ethoxycoumarin O-deethylase kinetics in isolated rat, dog and human hepatocyte suspensions

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Pages 231-241 | Received 05 Oct 1993, Published online: 27 Aug 2009
 

Abstract

1. A comparative study of the kinetics of the O-deethylation of 7-ethoxycoumarin has been carried out in freshly isolated rat, dog and human hepatocytes.

2. Biphasic kinetics were observed for all three species with apparent Km and Vmax values of 11.5, 2.2 and 3.9 μM and 0.30, 0.21, 0.007 nmol/min/106 cells from rat, dog and man, respectively, for the high affinity-low capacity component, and 560, 40, 470 μM and 1.52, 0.74, 0.057 nmol/min/106 cells, respectively, for the low affinity-high capacity component.

3. These observed kinetic parameters in hepatocytes from rat and man were similar to published values for microsomes for the same two species.

4. Values for intrinsic clearance of 7-ethoxycoumarin for the three species calculated from the Km and Vmax data were 152, 631 and 6 ml/min/kg for rat, dog and human hepatocytes, respectively. These intrinsic clearance values predict that 7-ethoxycoumarin would be subject to a high hepatic clearance in rat and dog, and low hepatic clearance in man. These values are supported by published data on rat which show that 7-ethoxycoumarin is subject to high clearance.

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