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活体肝移植受者中米卡芬净的最佳预防剂量及处置

Optimal prophylactic dosage and disposition of micafungin in living donor liver recipients.

作者信息

Kishino Satoshi, Ohno Keiko, Shimamura Tsuyoshi, Furukawatodo Hiroyukisatoru

机构信息

Department of Medication Use Analysis and Clinical Research, Meiji Pharmaceutical University, Tokyo, Japan.

出版信息

Clin Transplant. 2004 Dec;18(6):676-80. doi: 10.1111/j.1399-0012.2004.00272.x.

Abstract

Micafungin, a new candin antifungal drug, has a good safety profile and a significant therapeutic effect against Candida and Aspergillus. Little is known, however, about the optimal prophylactic dosage and the disposition of micafungin in liver transplant recipients, or about the effect of continuous venovenous hemodialysis (CVVH) on the pharmacokinetics of micafungin. Six living donor liver transplant patients were enrolled in this study. The mean C(max) and C(min) (trough) values of micafungin in plasma were 6.31 +/- 1.08 and 1.65 +/- 0.54 microg/mL, respectively. The mean elimination half-life (t(1/2)) and mean area under the curve up to 12 h post-dosing (AUC 0-12 h) were 13.63 +/- 2.77 h and 50.04 +/- 6.48 microg.h/mL, respectively. The concentrations of micafungin at the inlet and outlet of the dialyzer were very similar. The mean (+/-SD) ratio of micafungin concentrations at the inlet and outlet of the dialyzer (coutlet/cinlet) and the clearance of micafungin were 0.96 +/- 0.04 and 0.054 +/- 0.04 mL/min/kg, respectively. The amount in the ultrafiltrate was 1.0 mg. Micafungin effectively prevents systemic fungal infection in patients who have undergone liver transplantation. No significant differences were observed in the disposition of micafungin in recipients, and the therapeutic drug level can be achieved by administration of micafungin at a dosage of 40-50 mg/d. The CVVH had little effect on micafungin kinetics, and no dose adjustment or modification of dosing interval was needed during CVVH.

摘要

米卡芬净是一种新型棘白菌素类抗真菌药物,具有良好的安全性,对念珠菌和曲霉菌有显著的治疗效果。然而,对于肝移植受者中米卡芬净的最佳预防剂量、在体内的处置情况,以及连续性静脉-静脉血液透析(CVVH)对米卡芬净药代动力学的影响,人们了解甚少。本研究纳入了6例活体供肝移植患者。米卡芬净在血浆中的平均C(max)和C(min)(谷值)分别为6.31±1.08和1.65±0.54μg/mL。平均消除半衰期(t(1/2))和给药后12小时内的平均曲线下面积(AUC 0-12 h)分别为13.63±2.77小时和50.04±6.48μg·h/mL。透析器入口和出口处米卡芬净的浓度非常相似。透析器入口和出口处米卡芬净浓度的平均(±标准差)比值(coutlet/cinlet)以及米卡芬净的清除率分别为0.96±0.04和0.054±0.04 mL/min/kg。超滤液中的量为1.0 mg。米卡芬净可有效预防肝移植患者的系统性真菌感染。米卡芬净在受者体内的处置情况未观察到显著差异,通过给予40-50 mg/d的米卡芬净剂量可达到治疗药物水平。CVVH对米卡芬净的动力学影响很小,在CVVH期间无需调整剂量或给药间隔。

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