title: Effect of the cytochrome P450 2D6*10 genotype on the pharmacokinetics of tramadol in post-operative patients.
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.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: Xiang-Cai
authors.initials: XC
authors.lastname: Zhang
authors.forename: Xiao-Qin
authors.initials: XQ
authors.lastname: Lv
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Xu
authors.forename: Guo-Xiang
authors.initials: GX
authors.lastname: Wang
authors.forename: Bo
authors.initials: B
authors.lastname: Jiang
authors.forename: Long
authors.initials: L
authors.lastname: Cai
authors.forename: Xiu-Jun
authors.initials: XJ
authors.lastname: Cai
mesh_terms: D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005260:Female; D041981:Gastrointestinal Tract / Q000601:surgery; D005838:Genotype; D006207:Half-Life; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D010149:Postoperative Pain / Q000188:drug therapy / Q000378:metabolism*; D011110:Polymorphism, Genetic / Q000235:genetics; D014147:Tramadol / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D000701:Analgesics, Opioid; C080580:O-demethyltramadol; D014147:Tramadol; D019389:Cytochrome P-450 CYP2D6