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Journal of Pharmacology And Experimental Therapeutics, Vol. 189, Issue 1, 271-277, 1974
Copyright © 1974 by American Society for Pharmacology and Experimental Therapeutics

BUNOLOL METABOLISM BY HUMAN AND RAT RED BLOOD CELLS AND EXTRAHEPATIC TISSUES

Franz-Josef Leinweber 1 and Frederick J. Di Carlo 1

1 Department of Drug Metabolism, Warner-Lambert Research Institute, Morris Plains, New Jersey

A single metabolite was formed by incubating 14C-bunolol with cell-free preparations of human and rat erythrocytes. After purification by solvent extraction and preparative thin-layer chromatography, the metabolite was identified as dihydrobunolol by ultraviolet spectrometry and gas chromatography. At pH 7.1, bunolol was reduced rapidly by cell-free preparations of rat erythrocytes, but very slowly by cell-free preparations of human erythrocytes. The same erythrocyte extracts oxidized dihydrobunolol to bunolol; this reaction required the presence of nicotinamide adenine dinucleotide phosphate and did not proceed with nicotinamide adenine dinucleotide or in the absence of added cofactor. Human and rat blood plasma contained only very low concentrations of bunolol-reducing enzyme. Significant concentrations of bunolol-reducing enzyme were detected in rat heart, brain and lung. In terms of the capacity of the total organ, only the red blood cell fraction and the liver appear to be significant sites of dihydrobunolol formation.

Submitted on March 21, 1973
Accepted on December 10, 1973




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