CAJ | 학술논문

目的探讨肾移植受者长期服用五酯胶囊提高血他克莫司(Tac)浓度的安全性和适应证.方法将Tac浓度谷值相当的移植肾功能稳定的受者,根据是否长期服用五酯胶囊分为五酯组(10例)和对照组(10例),比较两组间Tac药动学参数,并比较五酯胶囊对不同细胞色素P450 3A5(CYP3A5)基因型受者服用Tac剂量的影响.结果五酯组服用五酯胶囊平均为31个月,平均Tac浓度谷值为6.3μg/L;对照组平均Tac浓度谷值为5.9 μg/L.五酯组平均Tac浓度峰值和曲线下面积均略高于对照组,达峰时间稍延迟,但差异无统计学意义(P＞0.05).CYP3A5* 1/*3型在二组中均占60％,而对照组中*1/*3型受者的Tac剂量为(0.067±0.001)mg· kg-1·d-1,明显高于五酯组同型受者的(0.042±0.016)mg·kg-1 ·d-1,差异有统计学意义(P＜0.01).*1/*1型受者在五酯组中占30％,其Tac剂量为(0.036±0.006)mg· kg-1·d-1,比*1/*3型受者减少更明显;平均剂量最低的为对照组*3/*3型受者,为(0.034±0.005)mg· kg-1·d-.结论对大部分CYP3A5*1基因型受者可以考虑应用五酯胶囊提升Tac浓度,尤其对CYP3A5*1/*1型受者.
목적 탐토신이식수자장기복용오지효낭제고혈타극막사(Tac)농도적안전성화괄응증.방법 장Tac농도곡치상당적이식신공능은정적수자,근거시부장기복용오지효낭분위오지조(10례)화대조조(10례),비교량조간Tac약동학삼수,병비교오지효낭대불동세포색소P450 3A5(CYP3A5)기인형수자복용Tac제량적영향.결과 오지조복용오지효낭평균위31개월,평균Tac농도곡치위6.3μg/L;대조조평균Tac농도곡치위5.9 μg/L.오지조평균Tac농도봉치화곡선하면적균략고우대조조,체봉시간초연지,단차이무통계학의의(P＞0.05).CYP3A5* 1/*3형재이조중균점60％,이대조조중*1/*3형수자적Tac제량위(0.067±0.001)mg· kg-1·d-1,명현고우오지조동형수자적(0.042±0.016)mg·kg-1 ·d-1,차이유통계학의의(P＜0.01).*1/*1형수자재오지조중점30％,기Tac제량위(0.036±0.006)mg· kg-1·d-1,비*1/*3형수자감소경명현;평균제량최저적위대조조*3/*3형수자,위(0.034±0.005)mg· kg-1·d-.결론 대대부분CYP3A5*1기인형수자가이고필응용오지효낭제승Tac농도,우기대CYP3A5*1/*1형수자.
Objective To determine the effect of Wuzhi capsule (WZ) on pharmacokinetics of Tacrolimus (Tac) in kidney transplant patients who have taken WZ to reduce the dose of Tac for a long term.Method Twenty stable renal transplant patients with similar trough level of Tac were divided into WZ group (n =10) and control group (n =10).Whole blood concentrations of Tac at 0,0.5,1,1.5,2,3,4,6,8 and 12 h after the morning dose was determined.Estimated pharmacokinetic parameters were calculated and compared.Additionally,CYP3A5 genotypes of each patient were analyzed using Polymerase Chain Reaction Restriction Fragment Length Polymorphism to compare the effect of CPY3A5 genotypes and WZ on Tac dose requirement.Result Pharmacokinetics data showed that Co of Tac was 6.3μg/L in WZ group and 5.9 μg/L in control group.The average peak time of Tac was similar (1.4 h in WZ group,and 1.3 h in control group,P＞0.05).Both the peak concentration of Tac and AUG0-12h of Tac were slightly higher in WZ group than in control group with the difference being not statistically significant.The frequency of CYP3A5 * 1/* 3 genotype was 60％ in both groups,while the average dose of Tac was reduced by 30％ in WZ group as compared with control group (0.042 mg·kg-1 ·day-1,and 0.067 mg·kg 1 ·day-1,P＜0.01).In WZ group,the average dose of Tac was even lower in carriers of * 1/* 1 genotype (0.036 mg·kg-1 ·day 1) than that in carriers of * 1/* 3 genotype,which was close to the lowest dose requirement in the carriers of * 3/* 3 genotype from the control group (0.034 mg·kg-1 day-1).Conclusion In kidney transplant patients with CYP3A5 * 1 genotype,a long-term application of WZ to reduce the required tacrolimus dose is a generally safe way without significant changes in regular pharmacokinetics of tacrolimus.For patients with genotype of CYP3A5 * 1/* 1,WZ is particularly suitable.