Dextromethorphan and mephenytoin phenotyping of patients treated with thioridazine or amitriptyline.

Details

Serval ID
serval:BIB_58AC4BC1DC67
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Dextromethorphan and mephenytoin phenotyping of patients treated with thioridazine or amitriptyline.
Journal
Therapeutic drug monitoring
Author(s)
Baumann P., Meyer J.W., Amey M., Baettig D., Bryois C., Jonzier-Perey M., Koeb L., Monney C., Woggon B.
ISSN
0163-4356 (Print)
ISSN-L
0163-4356
Publication state
Published
Issued date
02/1992
Peer-reviewed
Oui
Volume
14
Number
1
Pages
1-8
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
The metabolism of most tricyclic antidepressants and some phenothiazine neuroleptics is under the genetic control of hepatic cytochrome P-450IID6, which also regulates the metabolism of dextromethorphan. This study investigated the effect of treatment with amitriptyline or thioridazine on testing for genetically regulated efficiency of the metabolism of dextromethorphan and mephenytoin. One group of 33 patients was treated with 150 mg amitriptyline a day (the AMI group); 25 other patients received a daily dose of thioridazine, either 200 mg (200-THD group; n = 7) or 400 mg (400-THD group; n = 18). Before and after 10 days of this treatment, all patients were tested with 25 mg dextromethorphan and 100 mg mephenytoin to determine their pharmacogenetic status with respect to their hepatic drug oxidizing systems (cytochrome P-450IID6 and P-450 MP). Two patients were poor metabolizers (PMs) of dextromethorphan and three of mephenytoin. Treatment with either psychotropic drug was without significant effect on the metabolism of mephenytoin, but both amitriptyline and thioridazine increased significantly the metabolic ratio of dextromethorphan/dextrorphan. Thioridazine had the effect of changing the pharmacogenetic status of 15 efficient metabolizers of dextromethorphan to poor metabolizers; amitriptyline did not have such an effect. There was no significant correlation between day-11 plasma levels of thioridazine, mesoridazine, or sulforidazine and the metabolism of dextromethorphan, but there was a correlation between the metabolism of dextromethorphan and plasma levels of amitriptyline and nortriptyline. Amitriptyline (p less than 0.05), but not thioridazine, decreases the ratio of conjugated/total dextrorphan in urine.(ABSTRACT TRUNCATED AT 250 WORDS)
Keywords
Adult, Amitriptyline/blood, Amitriptyline/pharmacology, Aryl Hydrocarbon Hydroxylases, Cytochrome P-450 CYP2C19, Cytochrome P-450 CYP2D6, Cytochrome P-450 Enzyme System/metabolism, Dextromethorphan/pharmacokinetics, Dextromethorphan/urine, Female, Humans, Liver/enzymology, Male, Mephenytoin/pharmacokinetics, Mephenytoin/urine, Middle Aged, Mixed Function Oxygenases/metabolism, Phenotype, Thioridazine/blood, Thioridazine/pharmacology
Pubmed
Web of science
Create date
12/01/2021 16:16
Last modification date
15/04/2023 5:51
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