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01-03-2008 | Original Article

Correlation of inter-individual variations of amitriptyline metabolism examined in hairs with CYP2C19 and CYP2D6 polymorphisms

Authors: Detlef Thieme, Burkhard Rolf, Hans Sachs, Dagmar Schmid

Published in: International Journal of Legal Medicine | Issue 2/2008

Abstract

The metabolite ratio of amitriptyline (AT), nortriptyline (NT) and its 10-hydroxy metabolites (E10-OHAT, Z10-OHAT, E10-OHNT and Z10-OHNT) was examined by liquid chromatography-mass spectrometry in hair samples of 23 white infants after long-term administration of AT. High inter-individual variation of the metabolite ratios were observed (e.g. NT/AT = 0.8–8.1, E10-OHNT/Z10-OHNT = 1.6–10.3). The significance of these variations was proven by confirmation of the temporary stability of these ratios within a hair fibre. Moreover, an association of the metabolic phenotype with genetic disposition was observed. The genotypes of CYP2C19 (alleles *2, *3 and *4) and of CYP2D6 (*3, *4, and *6) were examined by conventional polymerase chain reaction genotyping experiments. The relative amount of demethylation (NT/AT) is clearly affected by the number of functional alleles of CYP2C19. The demethylation capacity of CYP2C19 poor metabolizers (3 individuals, compared to 15 extensive metabolizers) was 4.3 times depleted. Moreover, the selectivity of hydroxylation (e.g. E10-OHNT/Z10-OHNT) is significantly correlated with CYP2C19.

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Title: Correlation of inter-individual variations of amitriptyline metabolism examined in hairs with CYP2C19 and CYP2D6 polymorphisms
Authors: Detlef Thieme
Burkhard Rolf
Hans Sachs
Dagmar Schmid
Publication date: 01-03-2008
Publisher: Springer-Verlag
Published in: International Journal of Legal Medicine / Issue 2/2008
Print ISSN: 0937-9827
Electronic ISSN: 1437-1596
DOI: https://doi.org/10.1007/s00414-007-0184-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Correlation of inter-individual variations of amitriptyline metabolism examined in hairs with CYP2C19 and CYP2D6 polymorphisms

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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