E- and Z-10-hydroxylation of nortriptyline by human liver microsomes--methods and characterization

To enable in vitro characterization of nortriptyline 10-hydroxylase activity of microsomal fractions of human liver, methods for the determination of E- and Z-10-hydroxynortriptyline were developed. High performance liquid chromatography (HPLC) with UV-detection or HPLC separation followed by quanti...

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Bibliographic Details
Published inDrug metabolism and disposition Vol. 11; no. 2; p. 115
Main Authors Mellström, B, Bertilsson, L, Birgersson, C, Göransson, M, von Bahr, C
Format Journal Article
LanguageEnglish
Published United States 01.03.1983
Subjects
Adult
Aged
Cytochrome P-450 Enzyme System - metabolism
Female
Humans
Hydroxylation
In Vitro Techniques
Kinetics
Male
Microsomes, Liver - metabolism
Middle Aged
Nortriptyline - metabolism
Oxidation-Reduction
Stereoisomerism
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Summary:To enable in vitro characterization of nortriptyline 10-hydroxylase activity of microsomal fractions of human liver, methods for the determination of E- and Z-10-hydroxynortriptyline were developed. High performance liquid chromatography (HPLC) with UV-detection or HPLC separation followed by quantitation by gas chromatography-mass spectrometry were used. The microsomal 10-hydroxylation of nortriptyline was linear to 60 min with a protein concentration of 1 mg x ml-1. In 15 human livers a 5-fold variation in activity was found. The formation of the Z-isomer comprised 13 +/- 3% (mean +/- SD) of the total 10-hydroxylase activity. The 10-hydroxylation was inhibited by debrisoquine, sparteine, propranolol, and encainide. No effect or a stimulation of the activity was seen with p-nitroanisole and acetanilide.
ISSN:0090-9556