咪达唑仑在麻醉肝硬化患者中的药代动力学

Pharmacokinetics of midazolam in anaesthetized cirrhotic patients.

作者信息

Trouvin J H, Farinotti R, Haberer J P, Servin F, Chauvin M, Duvaldestin P

机构信息

Département d'Anesthésiologie, Hôpital Bichat, Paris, France.

出版信息

Br J Anaesth. 1988 Jun;60(7):762-7. doi: 10.1093/bja/60.7.762.

DOI:10.1093/bja/60.7.762

PMID:3395535

Abstract

The pharmacokinetics of midazolam were compared in cirrhotic patients (n = 10) and control patients (n = 9), during general anaesthesia. Total plasma clearance was 637 +/- 223 ml min-1 (mean +/- SD) in control patients and 402 +/- 170 ml min-1 in cirrhotic patients (P less than 0.05). The total volume of distribution was similar. Elimination half-life was 135 +/- 40 min in controls and 168 +/- 30 min in cirrhosis (P less than 0.05). Protein binding was evaluated by equilibrium dialysis in both groups at two concentrations of midazolam: 20 and 500 micrograms litre-1. No saturation occurred, but the free fraction was 4.9 +/- 1.7% in cirrhotic patients, compared with 1.9 +/- 0.6% in controls (P less than 0.01). Despite its mainly hepatic elimination, midazolam disposition appears to be only slightly impaired in cirrhotic patients.

摘要

在全身麻醉期间，对肝硬化患者（n = 10）和对照患者（n = 9）的咪达唑仑药代动力学进行了比较。对照患者的血浆总清除率为637±223 ml·min⁻¹（均值±标准差），肝硬化患者为402±170 ml·min⁻¹（P<0.05）。分布总体积相似。对照组的消除半衰期为135±40分钟，肝硬化患者为168±30分钟（P<0.05）。通过平衡透析在两组中对两种浓度的咪达唑仑（20和500微克/升）进行蛋白结合评估。未发生饱和现象，但肝硬化患者的游离分数为4.9±1.7%，而对照组为1.9±0.6%（P<0.01）。尽管咪达唑仑主要经肝脏消除，但在肝硬化患者中其处置似乎仅略有受损。