细胞色素P450 2D6* 10多态性对术后患者体内曲马多药动学特征的影响

Effect of cytochrome P450 2D6* 10 polymorphism on pharmacokinetic characteristic of tramadol in post-operative patients

目的研究细胞色素P450(CYP)2D6*10多态性对患者手术后应用曲马多止痛后体内曲马多药动学特征的影响。方法 45例患者于手术后首次静脉注射曲马多100 mg,随后采用LC-MS法测定曲马多及其代谢物O-去甲基曲马多(M1)的血浆浓度,采用非房室模型法计算曲马多和M1的主要药动学参数(AUC、CL、t1/2、MRT、ρmax和tmax)。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测患者的CYP2D6*10基因型,即野生型、杂合子和突变型。结果 45例患者中CYP2D6*10等位基因的发生频率为51%。与野生型比较,突变型患者体内曲马多的t1/2、MRT延长,AUC增大,CL减少(P均<0.05)。结论 CYP2D6*10基因多态性对术后患者体内曲马多的药动学特征有显著影响。

AIM To investigate the effects of cytochrome P450 （CYP）2D6 ＊ 10 on tramadol pharmacokinetic characteristic in post-operative patients who had undergone surgery. METHODS Tramadol was administered to 45 post- operative patients, and the plasma concentrations of tramadol and its metabolite O-desmethyltramadol （M1） were subse- quently determined by LC-MS method. Pharmacokinetic analyses were performed using non-compartmental methods. The area under the curve （AUC）, plasma clearance （CL）, elimination half-life （tl/2）, mean residence time （MRT）,Pmax and tmax of tramadol and M1 were calculated. CYP2D6 ~ 10 was genotyped by polymerase chain reaction-restriction frag- ment length polymorphism（PCR-RFLP） . RESULTS The frequency of CYP2D6 s 10 alleles was 51% in the 45 pa- tients. The patients were divided into 3 groups according to their CYP2D6 ＊10 genotypes： wild-type, heterozygous and homozygous mutant. Pharmacokinetic parameters were compared among the 3 groups. The analyses showed that tl/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）. CONCLUSION These results show that the CYP2D6 ~ 10 genetic polymorphism has a significant impacton the pharmacokinetic characteristic of tramadol in post-operative patients.