Pharmacokinetics of tramadol enantiomers and their respective phase I metabolites in relation to CYP2D6 phenotype

Pharmacokinetics of tramadol and its three main metabolites in healthy male and female volunteers

“…However, the difference between C max became significant and p values of AUCs changed in the case of M5. This is in agreement with the genetic polymorphism dependency of phase I metabolism of tramadol published recently [16].…”

Near-fatal tramadol cardiotoxicity in a CYP2D6 ultrarapid metabolizer

“…The marketed tramadol is a racemic mixture containing 50% of (+) tramadol and 50% of (-) tramadol, and is mainly metabolized to O-desmethyltramadol (M1) and N-desmethyltramadol (M2) by the cytochromes P450 CYP2B6/CYP3A4 and CYP2D6, respectively [1,2]. The pharmacokinetic and pharmacodynamic properties of tramadol are known to be both enantioselective and influenced by the CYP2D6 phenotype [1,[3][4][5][6]. The analgesic effect of tramadol is mainly due to morphinomimetic effects, the main metabolite of the CYP2D6 pathway, (+)-M1, showing the highest affinity for opioid receptors [1,7].…”

“…Genotyping analysis of CYP2D6, consisting of sequencing all exons with a previously described approach [9] and the detection of deletion/duplication alleles by TaqMan real-time PCR using a previously described method [4]. Moreover, the elevation in plasma epinephrine levels is highly correlated with the increase of (+)-M1 plasma concentration [4].…”

“…Genotyping analysis of CYP2D6, consisting of sequencing all exons with a previously described approach [9] and the detection of deletion/duplication alleles by TaqMan real-time PCR using a previously described method [4]. Moreover, the elevation in plasma epinephrine levels is highly correlated with the increase of (+)-M1 plasma concentration [4]. Consecutively to excessive tramadol ingestion, our patient, harboring a CYP2D6 UM phenotype and a partially inhibited CYP2B6 pathway, had probably experienced combined mechanisms that led to excessive circulating catecholamines.…”

Unerwünschte Nebenwirkungen von Tapentadol im Vergleich zu Oxycodon

“…Da allerdings nur 1 Metabolit des Tramadols (O-Desmethyltramadol) ein potenter Opioidagonist ist, ist die Aktivität des CYP2D6-Enzyms als transformierendes Enzymsystem maßgeblich an der hohen Variabilität der Tramadolwirkung beteiligt [9]. Dies betrifft ungefähr 5-15% der Patienten und ist damit sehr häufig [21].…”