edoc

Bufuralol metabolism in human liver : a sensitive probe for the debrisoquine-type polymorphism of drug oxidation

Minder, E. I. and Meier, P. J. and Müller, H. K. and Minder, C. and Meyer, U. A.. (1984) Bufuralol metabolism in human liver : a sensitive probe for the debrisoquine-type polymorphism of drug oxidation. European Journal of Clinical Investigation, Vol. 14, H. 3. S. 184-189.

Full text not available from this repository.

Official URL: http://edoc.unibas.ch/dok/A5261810

Downloads: Statistics Overview

Abstract

The genetically controlled polymorphism causing decreased metabolism of debrisoquine is closely related to that of the metabolism of bufuralol and numerous other drugs and has important clinical consequences. A sensitive in vitro assay was developed which quantifies the production of 1'-hydroxy-bufuralol (carbinol) from bufuralol in human liver microsomes. Initial formation rates of carbinol suggested Michaelis-Menten kinetics with an apparent KM of 61 and 171 mumol l-1 and Vmax of 3.2 and 5.8 nmol mg-1 microsomal protein h-1 in two human liver samples. The Vmax in microsomes of thirty-two liver samples was 4.2 +/- 1.0 (SD) nmol carbinol mg-1 protein h-1. Metabolism of debrisoquine in vivo, as expressed by the 'metabolic ratio' of debrisoquine over 4-OH debrisoquine correlated (r = -0.65, P less than 0.01; n = 18) with carbinol production rate in microsomes in vitro. Microsomes of one individual identified as poor metabolizer of debrisoquine in vivo showed reduction of carbinol formation to 1.97 nmol mg-1 h-1. Mixing his microsomes with those of an extensive metabolizer resulted in additive formation of carbinol excluding mediation of the defect by a soluble inhibitor. These data support the concept of a primary defect in microsomal oxidation of bufuralol. The described assay offers a sensitive tool to investigate the molecular mechanism of the 'debrisoquine polymorphism'.
Faculties and Departments:11 Rektorat und Verwaltung > Vizerektorat Forschung
UniBasel Contributors:Meier-Abt, Peter J.
Item Type:Article, refereed
Bibsysno:Link to catalogue
Publisher:Wiley
ISSN:0014-2972
e-ISSN:1365-2362
Note:Publication type according to Uni Basel Research Database: Journal article
Related URLs:
Identification Number:
Last Modified:13 Oct 2017 08:27
Deposited On:22 Mar 2012 13:39

Repository Staff Only: item control page