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一项关于亲属活体肝移植中他克莫司(FK506)最佳给药方案的提议。

A proposal of FK506 optimal dosing in living related liver transplantations.

作者信息

Ueda M, Uemoto S, Inomata Y, Okajima H, Hashida T, Tanaka K, Yamaoka Y

机构信息

Second Department of Surgery, Kyoto University Faculty of Medicine, Japan.

出版信息

Transplantation. 1995 Aug 15;60(3):258-64. doi: 10.1097/00007890-199508000-00009.

Abstract

We analyzed the relation between FK506 trough levels (ELISA: patients 1-41, IMx: patients 42-70) and rejection and/or viral infection episodes, retrospectively, in the first 70 consecutive cases of living related liver transplantation. Twenty patients (28.6%) had rejection episodes. Of the 13 patients who had evidence of rejection during the first 3 months, 6 patients without infection and 7 patients with viral infection showed low concentrations of FK506 (< 5 ng/ml). Twelve patients were treated and improved with high dose steroid administration and an increase in the FK506 dosage. One patient died of refractory rejection. Nine patients had evidence of rejection after the first 3 months. In 3 patients, weaning from FK506 initiated the rejection episodes. Five patients repeated rejection and 4 patients required a third immunosuppressant (azathioprine). Viral infection included CMV (11 cases), EBV (13 cases), HZV (3 cases), and HSV (1 case). Excess immunosuppression might have been the cause, but no clear correlation was found. We propose that the optimal dosage of FK506 obtained by monitoring the trough levels using the IMx method should maintain a 10-20 ng/ml level during the first month, and a 5-10 ng/ml level at the second and third months.

摘要

我们回顾性分析了连续70例亲属活体肝移植患者中,FK506谷浓度(酶联免疫吸附测定法:患者1 - 41例;免疫化学发光法:患者42 - 70例)与排斥反应和/或病毒感染发作之间的关系。20例患者(28.6%)发生了排斥反应。在最初3个月内有排斥反应证据的13例患者中,6例无感染且7例有病毒感染的患者FK506浓度较低(<5 ng/ml)。12例患者通过大剂量类固醇给药及增加FK506剂量进行治疗并好转。1例患者死于难治性排斥反应。9例患者在最初3个月后有排斥反应证据。在3例患者中,停用FK506引发了排斥反应发作。5例患者排斥反应复发,4例患者需要使用第三种免疫抑制剂(硫唑嘌呤)。病毒感染包括巨细胞病毒(11例)、EB病毒(13例)、带状疱疹病毒(3例)和单纯疱疹病毒(1例)。可能是免疫抑制过度导致,但未发现明确的相关性。我们建议,通过免疫化学发光法监测谷浓度获得的FK506最佳剂量,在第一个月应维持在10 - 20 ng/ml水平,在第二个月和第三个月应维持在5 - 10 ng/ml水平。

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