European Journal of Clinical Pharmacology

, Volume 43, Issue 4, pp 399–403 | Cite as

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

  • T. Graf
  • F. Broly
  • F. Hoffmann
  • M. Probst
  • U. A. Meyer
  • H. Howald
Originals

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.

Key words

Debrisoquine, Polymerase chain reaction pharmacogenetics, genotype-phenotype, caffeine 

Abbreviations

PM

poor metabolizer

EM

extensive metabolizer

MR

metabolic ratio

RFLP

restriction fragment length polymorphism

PCR

polymerase chain reaction

D6-A, D6-B, D6-C, D6-D

defined mutations of the CYP2D6 gene

M1, M2, M3

defined mutations of the NAT2 gene

D6-wt

D6-wild type

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Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • T. Graf
    • 1
  • F. Broly
    • 2
  • F. Hoffmann
    • 2
  • M. Probst
    • 2
  • U. A. Meyer
    • 2
  • H. Howald
    • 1
  1. 1.Human Pharmacology Unit, Department of Research and DevelopmentPharmaceutical Division of Ciba-Geigy Ltd.BaselSwitzerland
  2. 2.Department of PharmacologyBiocenter of the University of BaselBaselSwitzerland

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