中华麻醉学杂志
中華痳醉學雜誌
중화마취학잡지
CHINESE JOURNAL OF ANESTHESIOLOGY
2008年
8期
677-679
,共3页
虞建刚%王俊科%李平%孙新艳%王秋石
虞建剛%王俊科%李平%孫新豔%王鞦石
우건강%왕준과%리평%손신염%왕추석
细胞色素P450CYP 2D6%多态性,单核苷酸%曲马朵%药代动力学
細胞色素P450CYP 2D6%多態性,單覈苷痠%麯馬朵%藥代動力學
세포색소P450CYP 2D6%다태성,단핵감산%곡마타%약대동역학
Cytochrome P-450 CYP2D6%Polymorphism,single nucleotide%Tramadol%Pharmacokinetics
目的 探讨细胞色素P450 2D6*10(CYP2D6*10)基因多态性对曲马多药代动力学的影响.方法 辽宁籍汉族健康志愿者,性别不限,年龄22～45岁,体重50～82 kg,身高161～179 cm,经左肘静脉采血2 ml,采用酚/氯仿抽提法提取全血DNA,采用聚合酶链反应.限制性片段长度多态性进行CYP2D6*10基因分型,分为野生型纯合子组(w/w组,n=5)、杂合子组(m/w组,n=8)和突变型纯合子组(m/m组,n=6).右上肢静脉经3 min注射曲马多1.5 ms/kg.分别于注射前、注射后0.25、0.5、1、1.5、2、3、4、6、8、12、16、24、32 h时取血3 ml,测定血浆曲马多及O-去甲基曲马多浓度.采用非房室模型方法计算曲马多曲线下面积(AUG0→∞)、血浆清除率(CL)、血浆消除半衰期(t1/2)、平均滞留时间(MRT)、血浆代谢率(MR)和0-去甲基曲马多峰浓度(Cmax)、达峰时间(Tmax)、AUc..、MRT.结果 与w/w组比较,m/m组曲马多t..和MRT延长,MR降低,O.去甲基曲马多AUC0→∞减少,m/w组曲马多MR降低(P<0.05或0.01);与m/m组比较,m/w组曲马多MR降低(P<0.01).结论 CYP2D6*10基因多态性是引起曲马多药代动力学个体差异的重要遗传因素之一.
目的 探討細胞色素P450 2D6*10(CYP2D6*10)基因多態性對麯馬多藥代動力學的影響.方法 遼寧籍漢族健康誌願者,性彆不限,年齡22～45歲,體重50～82 kg,身高161～179 cm,經左肘靜脈採血2 ml,採用酚/氯倣抽提法提取全血DNA,採用聚閤酶鏈反應.限製性片段長度多態性進行CYP2D6*10基因分型,分為野生型純閤子組(w/w組,n=5)、雜閤子組(m/w組,n=8)和突變型純閤子組(m/m組,n=6).右上肢靜脈經3 min註射麯馬多1.5 ms/kg.分彆于註射前、註射後0.25、0.5、1、1.5、2、3、4、6、8、12、16、24、32 h時取血3 ml,測定血漿麯馬多及O-去甲基麯馬多濃度.採用非房室模型方法計算麯馬多麯線下麵積(AUG0→∞)、血漿清除率(CL)、血漿消除半衰期(t1/2)、平均滯留時間(MRT)、血漿代謝率(MR)和0-去甲基麯馬多峰濃度(Cmax)、達峰時間(Tmax)、AUc..、MRT.結果 與w/w組比較,m/m組麯馬多t..和MRT延長,MR降低,O.去甲基麯馬多AUC0→∞減少,m/w組麯馬多MR降低(P<0.05或0.01);與m/m組比較,m/w組麯馬多MR降低(P<0.01).結論 CYP2D6*10基因多態性是引起麯馬多藥代動力學箇體差異的重要遺傳因素之一.
목적 탐토세포색소P450 2D6*10(CYP2D6*10)기인다태성대곡마다약대동역학적영향.방법 료녕적한족건강지원자,성별불한,년령22～45세,체중50～82 kg,신고161～179 cm,경좌주정맥채혈2 ml,채용분/록방추제법제취전혈DNA,채용취합매련반응.한제성편단장도다태성진행CYP2D6*10기인분형,분위야생형순합자조(w/w조,n=5)、잡합자조(m/w조,n=8)화돌변형순합자조(m/m조,n=6).우상지정맥경3 min주사곡마다1.5 ms/kg.분별우주사전、주사후0.25、0.5、1、1.5、2、3、4、6、8、12、16、24、32 h시취혈3 ml,측정혈장곡마다급O-거갑기곡마다농도.채용비방실모형방법계산곡마다곡선하면적(AUG0→∞)、혈장청제솔(CL)、혈장소제반쇠기(t1/2)、평균체류시간(MRT)、혈장대사솔(MR)화0-거갑기곡마다봉농도(Cmax)、체봉시간(Tmax)、AUc..、MRT.결과 여w/w조비교,m/m조곡마다t..화MRT연장,MR강저,O.거갑기곡마다AUC0→∞감소,m/w조곡마다MR강저(P<0.05혹0.01);여m/m조비교,m/w조곡마다MR강저(P<0.01).결론 CYP2D6*10기인다태성시인기곡마다약대동역학개체차이적중요유전인소지일.
Objective To investigate the effect of eytochrome P450 2D6* 10 (CYP2D6* 10) genetic polymorphism on tramadol pharmacokinetics. Methods Nineteen healthy volunteers from Liaoning province aged 22-45 yr weighing 50-82 kg height 161-179 cm were enrolled in this study. Blood samples were taken from left ulnar vein for DNA extraction and CYP2D6* 10 genotyping using phenol chloroform extracting method and polymerase chain reaction-restriction fragment length polymorphism respectively. The volunteers were divided into 3 groups according to their genotypes: wild hemozygote group (w/w), heterozygote group (m/w) and mutation homozygote group (m/m). Tramadol 1.5 mg/kg was injected intravenously over 3 rain through a vein in right upper extremity. Blood samples were taken before tramadol injection and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32 h after injection for determination of plasma tramadol and O-demethyl tramadol concentration by high-performance liquid chromatography. Pharmacokinetie analysis was performed using nonparametric methods. Area under concentration curve (AUC0→∞), plasma clearance (CL), elimination half-life (t1/2) and mean residence time (MRT) and metabolic rate (MR) of tramedol and peak concentration (Cmax) peak time (Tmax), AUC0→∞ and MRT of O-demethyl tramadol were calculated. Results MR of tramadol was significantly lower in m/w and m/m group, t1/2 and MRT of tramadol were significantly longer in m/m group and AUC0→∞ of O-demethyl tramadol was significantly lower in m/m group than in w/w group. MR of tramadol was significantly higher in m/w group than in m/m group. Conclusion CYP2D6* 10 genetic polymorphism is one of the genetic factors producing individual variation in tramadol pharmacokinetics.
