中华器官移植杂志
中華器官移植雜誌
중화기관이식잡지
CHINESE JOURNAL OF ORGAN TRANSPLANTATION
2015年
1期
1-6
,共6页
陈奕宽%薛峰%沈丛欢%韩龙志%周韬%杨太华%卢军%张建军%夏强
陳奕寬%薛峰%瀋叢歡%韓龍誌%週韜%楊太華%盧軍%張建軍%夏彊
진혁관%설봉%침총환%한룡지%주도%양태화%로군%장건군%하강
细胞色素P450 CYP3A5%他克莫司%药代动力学%婴儿%肝移植
細胞色素P450 CYP3A5%他剋莫司%藥代動力學%嬰兒%肝移植
세포색소P450 CYP3A5%타극막사%약대동역학%영인%간이식
Cytochrome P-450 CYP3A5%Tacrolimus%Pharmacokinetics%Infant%Liver transplantation
目的 研究婴幼儿肝移植供、受者的CYP3A5基因型对他克莫司(Tac)药动学的影响,从而建立适合婴幼儿肝移植受者的适合给药方案.方法 将85对肝移植供者和婴幼儿受者根据CYP3A5基因型分为4组:受者表达/供者表达组(EX-R/EX-D组)27例,受者表达/供者不表达组(EX-R/NEX-D组)10例,受者不表达/供者表达组(NEX-R/EX-D组)15例,受者不表达/供者不表达组(NEX-R/NEX-D组)33例.比较并分析各组的Tac服用剂量和血药浓度/剂量值的相关性.结果 NEX-R/NEX-D组受者Tac初始剂量为(0.19±0.08)mg·kg-1 ·d-1,与之相比较,EX-R/EX-D组受者的Tac初始剂量更高,为(0.26±0.09)mg· kg-1·d-1(P＜0.01),此后直到术后12个月后者Tac剂量始终较高.且EX-R/EX-D组受者的血Tac浓度达峰时间更长、药物代谢更快.CYP3A5基因型对于Tac代谢(即血药浓度/剂量)具有显著影响作用,占到36.85％,其中供者的CYP3A5基因型占主要作用,达到30.56％(P＜0.01).结论 肝移植术后受者Tac服用剂量的个体化差异与供、受者的CYP3A5基因多态性密切相关,术前检测供、受者的CYP3A5基因型可以预测肝移植术后Tac药动学,为Tac个体化用药提供可靠的参考指标.对于EX-R/EX-D受者Tac初始剂量可以为0.25～0.30 mg·kg-1 ·d-1.
目的 研究嬰幼兒肝移植供、受者的CYP3A5基因型對他剋莫司(Tac)藥動學的影響,從而建立適閤嬰幼兒肝移植受者的適閤給藥方案.方法 將85對肝移植供者和嬰幼兒受者根據CYP3A5基因型分為4組:受者錶達/供者錶達組(EX-R/EX-D組)27例,受者錶達/供者不錶達組(EX-R/NEX-D組)10例,受者不錶達/供者錶達組(NEX-R/EX-D組)15例,受者不錶達/供者不錶達組(NEX-R/NEX-D組)33例.比較併分析各組的Tac服用劑量和血藥濃度/劑量值的相關性.結果 NEX-R/NEX-D組受者Tac初始劑量為(0.19±0.08)mg·kg-1 ·d-1,與之相比較,EX-R/EX-D組受者的Tac初始劑量更高,為(0.26±0.09)mg· kg-1·d-1(P＜0.01),此後直到術後12箇月後者Tac劑量始終較高.且EX-R/EX-D組受者的血Tac濃度達峰時間更長、藥物代謝更快.CYP3A5基因型對于Tac代謝(即血藥濃度/劑量)具有顯著影響作用,佔到36.85％,其中供者的CYP3A5基因型佔主要作用,達到30.56％(P＜0.01).結論 肝移植術後受者Tac服用劑量的箇體化差異與供、受者的CYP3A5基因多態性密切相關,術前檢測供、受者的CYP3A5基因型可以預測肝移植術後Tac藥動學,為Tac箇體化用藥提供可靠的參攷指標.對于EX-R/EX-D受者Tac初始劑量可以為0.25～0.30 mg·kg-1 ·d-1.
목적 연구영유인간이식공、수자적CYP3A5기인형대타극막사(Tac)약동학적영향,종이건립괄합영유인간이식수자적괄합급약방안.방법 장85대간이식공자화영유인수자근거CYP3A5기인형분위4조:수자표체/공자표체조(EX-R/EX-D조)27례,수자표체/공자불표체조(EX-R/NEX-D조)10례,수자불표체/공자표체조(NEX-R/EX-D조)15례,수자불표체/공자불표체조(NEX-R/NEX-D조)33례.비교병분석각조적Tac복용제량화혈약농도/제량치적상관성.결과 NEX-R/NEX-D조수자Tac초시제량위(0.19±0.08)mg·kg-1 ·d-1,여지상비교,EX-R/EX-D조수자적Tac초시제량경고,위(0.26±0.09)mg· kg-1·d-1(P＜0.01),차후직도술후12개월후자Tac제량시종교고.차EX-R/EX-D조수자적혈Tac농도체봉시간경장、약물대사경쾌.CYP3A5기인형대우Tac대사(즉혈약농도/제량)구유현저영향작용,점도36.85％,기중공자적CYP3A5기인형점주요작용,체도30.56％(P＜0.01).결론 간이식술후수자Tac복용제량적개체화차이여공、수자적CYP3A5기인다태성밀절상관,술전검측공、수자적CYP3A5기인형가이예측간이식술후Tac약동학,위Tac개체화용약제공가고적삼고지표.대우EX-R/EX-D수자Tac초시제량가이위0.25～0.30 mg·kg-1 ·d-1.
Objective Little irnforrnation is available regarding the impact of cytochrome P450 (CYP) 3A5 on the metabolism of tacrolimus (TAC) in ifant liver transplantation.Therefore,the CYP3A5 genotype of Chinese pediatric recipients (intestine) as well as donors (graft liver) was analysed for the purpose of establishing an optimal dosage regimen in children.Method Eighty-five patients treated with TAC were divided into the following groups according to CYP3A5 genotype [expression of * 1 allele:expression (EX) and non-expression (NEX)] for each recipient (R) and donor (D):EX-R/EX-D (n =27),EX-R/NEX-D (n =10),NEX-R/EX-D (n =15) and NEX-R/NEX-D (n =33).TAC daily dose requirement and concentration/dose ratios were analyzed.Result Initial TAC daily dose requirement was higher among EX-R/EX-D children than in those who didn't express CYP3A5 (0.26 ± 0.09 vs 0.19 ± 0.08mg·kg-1 ·d-1,P＜0.01).CYP3A5 expression contributed an overall of 36.85％ to its concentration/dose ratios,and graft liver was a key determinant (30.56％,P＜0.01).Conclusion CYP3A5 genotype in both recipients and donors significantly affects TAC pharmacokinetics after liver transplantation in pediatric patients.Pre-operative assessment of CYP3A5 genotypes in both recipients and donors may be important to predict TAC pharmacokinetics,and administration of this drug using the appropriate dose and schedule can achieve the maximum benefit to patients.We suggest that pediatric patients carrying EX-R/EX-D genotype should be given a higher initial dosage of TAC (0.25-0.3 mg·kg-1 ·d-1) in the early stage post-LTx.
