P450 3A activity and cyclosporine dosing in kidney and heart transplant recipients.
P450 3A activity and cyclosporine dosing in kidney and heart transplant recipients.
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肾移植和心脏移植受者中的 P450 3A 活性和环孢素剂量。
DOI：
10.1038/clpt.1994.135
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发表时间：
1994
影响因子：
6.7
通讯作者：
Watkins,PB
中科院分区：
文献类型：
--
作者：
Turgeon,DK;Leichtman,AB;Lown,KS;Normolle,DP;Deeb,GM;Merion,RM;Watkins,PB
环孢素动力学的患者间差异似乎部分来自称为P450 3A的酶的催化活性的个体间差异。我们研究了P450 3A活性之间的关系，通过红霉素呼吸试验（ERMBT）测量，和目前由我们机构的医生确定的环孢素的适当稳定的每日剂量。ERMBT用于肾和心脏移植受者，这些受者至少参加了两次每月一次的门诊访视，而其每日环孢素剂量没有改变。在心脏（r= 0.68;p= 0.04;n= 9）和肾脏（r= 0.68;p = 0.03;n= 10）受体中，ERMBT结果与每日环孢素剂量（mg/kg）之间存在显著正相关。为了证实我们的研究结果，我们前瞻性地对20例接受肾移植的患者多次给予ERMBT。尽管移植医生对ERMBT结果不知情，但该测试预测了他们最终为患者开出的稳定的环孢素每日剂量（r= 0.54;p= 0.015）。当将所有39例患者的数据汇总并进行多元回归分析时，ERMBT是唯一与稳定的每日环孢素剂量显著相关的变量（r = 0.63;p <0.001;n= 39）。在前瞻性研究的20例患者中，术后数月内环孢素的处方日剂量通常会降低，环孢素日剂量的百分比变化与此期间P450 3A活性的变化相关（r =0.47;p= 0.03）。我们得出结论，P450 3A活性的患者间和患者内差异部分解释了移植医生环孢霉素给药的做法。临床药理学和治疗学（1994）56，253 -260; doi：10.1038/clpt.1994.135
Interpatient differences in the kinetics of cyclosporine appear to result in part from interindividual differences in the catalytic activity of an enzyme termed P450 3A. We investigated the relationship between P450 3A activity, as measured by the erythromycin breath test (ERMBT), and the appropriate stable daily dose of cyclosporine as currently determined by physicians at our institution. The ERMBT was administered to kidney and heart allograft recipients who had attended at least two monthly clinic visits without having their daily cyclosporine dose changed. There was a significant positive correlation between the ERMBT result and the daily cyclosporine doses (in milligrams per kilogram) in both the heart (r= 0.68;p= 0.04;n= 9) and kidney (r= 0.68;p= 0.03;n= 10) recipients. To confirm our findings, we prospectively administered the ERMBT on multiple occasions to 20 patients who were undergoing kidney transplantation. Although the transplant physicians were blinded to the ERMBT results, the test predicted the stable daily doses of cyclosporine that they ultimately prescribed to the patients (r= 0.54;p= 0.015). When data from all 39 patients were pooled and subjected to multiple regression analysis, the ERMBT was the only variable examined that significantly correlated with the stable daily cyclosporine dose (r = 0.63;p <0.001;n= 39). In the 20 patients prospectively studied, the prescribed daily dose of cyclosporine generally decreased during the months after surgery and the percentage changes in cyclosporine daily dose correlated with changes in P450 3A activity during this period (r =0.47;p= 0.03). We conclude that interpatient and intrapatient differences in P450 3A activity in part account for the cyclosporine dosing practices of transplant physicians.Clinical Pharmacology and Therapeutics(1994)56,253–260; doi:10.1038/clpt.1994.135