Miotic action of tramadol is determined by CYP2D6 genotype

Title:

Miotic action of tramadol is determined by CYP2D6 genotype

Creator:

Ondřej Slanař, Milan Nobilis, Jaroslav Květina, Rudolf Mikoviny, Tomáš Zima, Jeffrey R. Idle, and František Perlík

Identifier:

https://cdk.lib.cas.cz/client/handle/uuid:2e0674d7-e9d6-4c44-b622-faa29fabe4ce
uuid:2e0674d7-e9d6-4c44-b622-faa29fabe4ce
issn:0862-8408

Subject:

Farmacie. Farmakologie, farmakokinetika, cytochromy, genotyp, pharmacokinetics, cytochromes, genotype, cytochrom P450 2D6, miosa, tramadol, cytochrome P450 2D6, miosis, 14, and 615

Type:

article, články, model:article, and TEXT

Format:

print, bez média, and svazek

Description:

Polymorphic CYP2D6 is the enzyme that activates the opioid analgesic tramadol by O-demethylation to its active metabolite O-demethyltramadol (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 poor metabolizers (PM) 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 PM subjects by an almost threefold greater (P=0.0014) 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 (p‹0.01). 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., O. Slanař, M. Nobilis, J. Květina, R. Mikoviny, T. Zima, J. R. Idle, F. Perlík., and Obsahuje biblografii a bibliografické odkazy

Language:

English

Rights:

http://creativecommons.org/licenses/by-nc-sa/4.0/
policy:public

Source:

Physiological research | 2007 Volume:56 | Number:1

Harvested from:

CDK

Metadata only:

false