Effect of the cytochrome P450 2D6*10 genotype on the pharmacokinetics of tramadol in post-operative patients.

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Xu J, Zhang XC, Lv XQ, Xu YY, Wang GX, Jiang B, Cai L, Cai XJ

Effect of the cytochrome P450 2D6*10 genotype on the pharmacokinetics of tramadol in post-operative patients.

Pharmazie. 2014 Feb;69(2):138-41.

PubMed ID

24640604 [ View in PubMed

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Abstract

The cytochrome P450 2D6 (CYP2D6) is the most highly polymorphic isoenzyme of the cytochrome P-450-system, which affects the metabolism of one-fourth of all prescription drugs. Tramadol, a narcotic-like pain reliever used to treat moderate to severe pain, is primarily metabolized by CYP2D6. The CYP2D6*10 allele is the most common allele in the Chinese population. Therefore, we investigated the effects of CYP2D6*10 on tramadol pharmacokinetics in 45 post-operative patients who had undergone gastrointestinal tract surgery. Tramadol was administered to the patients after the operation, and the plasma concentrations of tramadol and O-desmethyltramadol were subsequently evaluated at 12 time points. Pharmacokinetic analyses were performed using non-compartmental methods. The area under the curve (AUC), plasma clearance (CL), elimination half-life (T1/2), mean residence time (MRT), peak concentration, and peak time of tramadol and O-desmethyltramadol were calculated. CYP2D6*10 was genotyped by polymerase chain reaction-restriction fragment length polymorphism. The frequency of CYP2D6*10 alleles was 51% in the 45 patients. The patients were divided into three groups according to their CYP2D6*10 genotype: wild-type, heterozygous, and homozygous mutant. Pharmacokinetic parameters were compared among the three groups. The analyses showed that T1/2, MRT, and AUC of tramadol were larger, and CL was lower in homozygous mutant patients compared to the wild-type group (P< 0.05). These results show that the CYP2D6*10 genetic polymorphism has a significant impact on the pharmacokinetics of tramadol in Chinese post-operative patients.

DrugBank Data that Cites this Article

Drugs

Tramadol

Pharmaco-genomics

Drug	Interacting Gene/Enzyme	Allele name	Genotypes	Defining change(s)	Type(s)	Description	Details
Tramadol	Cytochrome P450 2D6 Gene symbol: CYP2D6 UniProt: P10635	CYP2D6*10	Not Available	100C>T (but also appears in other variants) (rs1065852)	ADR pgx review	This mutation leads to an unstable CYP2D6 enzyme with lower metabolic activity.	Details