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

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 CYP2D610 allele is the most common allele in the Chinese population. Therefore, we investigated the effects of CYP2D610 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. CYP2D610 was genotyped by polymerase chain reaction-restriction fragment length polymorphism. The frequency of CYP2D610 alleles was 51% in the 45 patients. The patients were divided into three groups according to their CYP2D610 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 CYP2D610 genetic polymorphism has a significant impact on the pharmacokinetics of tramadol in Chinese post-operative patients.