Effects Of Cytochrome P4502D6~*10Gene Polylmorphisms On The Pharmacokinetics And Pharmacodynamics Of Tramadol In Postoperative Patients

Objective:The cytochrome P450gene encodes the CYP superfamily of enzymes, which affect 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. CYP2D6polymorphisms affect the pharmacokinetics and pharmacodynamics of tramadol. The CYP2D6*10allele is the most common allele in Chinese populations. The postoperative patients were investigated to reveal the effects of P4502D6*10on tramadol and M1pharmacokinetics.Methods:Forty-five subjects scheduled for gastrointestinal tract operation were included in this study. Blood samples were taken to detect the genotyping of CYP2D6*10gene duplication allele by the polymerase chain reaction-restriction fragment length polymorphism. x2test analysis of genotype frequencies is tested to make sure if the subjects were in Hardy-Weinberg equilibrium. Tramadol100mg was injected intravenously in the postoperative patients and the plasma concentrations of tramadol and O-desmethyltramadol were subsequently evaluated at12time points, respectively. We use non-compartmental methods to analyse pharmacokinetic data. The peak concentration, area under the curve (AUC), elimination half-life (T1/2), peak time plasma clearance (CL), and mean residence time (MRT) of tramadol and O-desmethyltramadol were calculated. Three groups were divided according to their P4502D6*10genotypes:wild-type, heterozygous, and homozygous mutant. Pharmacokinetic parameters were compared among the three groups.Results:x2test analysis of genotype frequencies confirmed that the subjects were in Hardy-Weinberg equilibrium The AUC0-∞;T1/2,and MRT of tramadol were larger in patients with mutation homozygote (m/m group) than patients with wild homozygosis (w/w group)(p<0.05), Cmaxwas higher, CL and Tmax was lower (p>0.05).In patients with w/w and m/m, T1/2of O-demethyl tramadol were short and AUCo-∞were lower (p>0.05) compare with w/m.. And CL was higher in the patients with w/w (p>0.05). T1/2, AUC0-∞and MRT of tramadol were statistically significant difference between w/w and m/m groups (p<0.05).Conclusion:CYP2D6*10genetic polymorphism is one of the genetic factors producing individual variation in tramadol pharmacokinetics. Part2Effects of cytochrome P4502D6*10gene polymorphisms on pharmacodynamics of tramadol in postoperative patientsObjective:Individual susceptibility to pain and its treatment is to some extent determined by polymorphism of drug-metabolizing enzymes, such as the cytochromes P450(CYPs). The cytochrome P450gene encodes the CYP superfamily of enzymes, which affect 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 analgesic effect of the metabolin M1is6times than tromadol. CYP2D6polymorphisms affect the pharmacokinetics and pharmacodynamics of tramadol. The CYP2D6*10allele is the most common allele in Chinese populations. In this study, we try to decrease the effects of other drugs on patients pain evaluation. Therefore, we investigated the effects of CYP2D6*10on tramadol pharmacodynamic in postoperative patients.Methods:forty-five patients scheduled anesthesia abortion were included in this study Blood samples were taken to detect the genotyping of CYP2D6*10gene duplication allele by the polymerase chain reaction-restriction fragment length polymorphism.χ2test analysis of genotype frequencies is tested to make sure if the subjects were in Hardy-Weinberg equilibrium.All patients received a standardized anesthetic plan with tramadol and propofol. Pain intensity scores were recorded at7points until24hours postoperatively. Side effects and satisfaction rate were recorded.Results:χ2test analysis of genotype frequencies confirmed that the subjects were in Hardy-Weinberg equilibrium(χ2=3.53, p>0.05). The VNRS score was higher in mutation homozygote group than in wild homozygosis group and heterozygote group(p<0.05). The incidence rate of nausea in the mutation homozygote group is similar with that of in the wild homozygosis group and heterozygote group.Conclusion:CYP2D6*10genetic polymorphism is one of the genetic factors producing individual variation in tramadol pharmacodynamics.