Prediction of phenotype for acetylation and for debrisoquine hydroxylation by DNA-tests in healthy human volunteers

The debrisoquine/sparteine-type polymorphism of drug oxidation and the polymorphism for acetylation are two common inherited variations in human drug metabolism. The phenotypes for hydroxylation and acetylation can be predicted be newly developed methods based on mutation-specific amplification of D...

Full description

Saved in:
Bibliographic Details
Published in:European journal of clinical pharmacology 1992-10, Vol.43 (4), p.399-403
Main Authors: GRAF, T, BROLY, F, HOFFMANN, F, PROBST, M, MEYER, U. A, HOWALD, H
Format: Article
Language:English
Subjects:
Acetylation
Adult
Biological and medical sciences
Debrisoquin - metabolism
Female
Gene Amplification
General pharmacology
Genotype
Humans
Hydroxylation
Male
Medical sciences
Middle Aged
Mutation
Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions
Pharmacology. Drug treatments
Phenotype
Polymerase Chain Reaction
Polymorphism, Genetic - genetics
Sparteine - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The debrisoquine/sparteine-type polymorphism of drug oxidation and the polymorphism for acetylation are two common inherited variations in human drug metabolism. The phenotypes for hydroxylation and acetylation can be predicted be newly developed methods based on mutation-specific amplification of DNA by the polymerase chain reaction (PCR), which also allow for identification of heterozygous carriers of one mutant allele. In the present study, the results of genotyping of 81 healthy European volunteers were compared with the phenotype obtained by the classical biochemical approach using debrisoquine and caffeine as probe drugs. Genotyping correctly predicted all 73 extensive metabolisers (EMs) and 6 out of 8 poor metabolisers (PMs) of debrisoquine. All 48 rapid acetylators and 33 of 35 slow acetylators were predicted. Overall, the DNA analysis result matched the in vivo phenotype in 97.5% of individuals.
ISSN:0031-6970
1432-1041
DOI:10.1007/bf02220616