Miotic action of tramadol is determined by CYP2D6 genotype

Slanar, O; Nobilis, M; Kvetina, J; Mikoviny, R; Zima, T; Idle, J R; Perlík, F (2006). Miotic action of tramadol is determined by CYP2D6 genotype. Physiological research, 56(1), pp. 129-136. Praha: Academia Scientiarum Bohemoslovaca

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Polymorphic CYP2D6 is the enzyme that activates the opioid analgesic tramadol by O-demethylation to M1. Our objective was to determine the opioid effects measured by pupillary response to tramadol of CYP2D6 genotyped volunteers in relation to the disposition of tramadol and M1 in plasma. Tramadol displayed phenotypic pharmacokinetics and it was possible to identify PM subjects with >99% confidence from the metabolic ratio (MR) in a single blood sample taken between 2.5 and 24 h post-dose. Homozygous extensive metabolizers (EM) differed from poor metabolizers (PM), with an almost three-fold greater (P=0.0014) mean maximal pupillary constriction (Emax). Significant correlations between the AUC and Cmax values of M1 versus pupillary constriction were found. The corresponding correlations of pharmacokinetic parameters for tramadol itself were weaker and negative. The strongest correlations were for the single-point metabolic ratios at all sampling intervals versus the effects, with rs ranging from 0.85 to 0.89 (p0.01). It is concluded that the concept of dual opioid/non-opioid action of the drug, though considerably stronger in EMs, is valid for both EM and PM subjects. This is the theoretical basis for the frequent use and satisfactory efficacy of tramadol in clinical practice when given to genetically non-selected population.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Clinical Pharmacology and Visceral Research [discontinued]

UniBE Contributor:

Idle, Jeffrey

ISSN:

0862-8408

ISBN:

16497087

Publisher:

Academia Scientiarum Bohemoslovaca

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:45

Last Modified:

08 Jun 2016 10:38

PubMed ID:

16497087

Web of Science ID:

000246657100014

URI:

https://boris.unibe.ch/id/eprint/18588 (FactScience: 783)

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