Bolon M, Bastien O, Flamens C, Paulus S, Boulieu R
Université Claude Bernard Lyon 1, Institut des Sciences Pharmaceutiques et Biologiques, Département de Pharmacie clinque, de Pharmacocinétique et d'Evaluation du Médicament, France.
J Clin Pharmacol. 2001 Sep;41(9):959-62. doi: 10.1177/00912700122010933.
The aim of the study was to investigate the pharmacokinetics and removal of midazolam and unconjugated and glucuronidated 1-hydroxy-midazolam in 4 intensive care patients on continuous venovenous hemodialysis. Plasma midazolam and its metabolites were assessed by HPLC from blood samples collected during continuous infusion and after the end of infusion. Additional samples from the arterial and venous bloodlines and ultrafiltrate were drawn to calculate sieving coefficient and clearance of ultrafiltration. The elimination half-life of midazolam ranged from 7.6 to 22.8 hours. The clearance of ultrafiltration was between 0.13 and 4.7 ml/min and reached approximately 11% of the total clearance. The range of sieving coefficient was from 0.006 to 0.26, with an average fraction removal of 0.2%. 1-Hydroxy-midazolam glucuronide was removed by continuous hemodialysis (sieving 0.36 to 0.63), with a clearance of ultrafiltration ranging from 7.8 to 12.0 ml/min. These preliminary results showed that midazolam is not removed efficiently, and approximately half of the 1-hydroxy-midazolam glucuronide was removed by dialysis.
该研究的目的是调查4例接受持续静静脉血液透析的重症监护患者中咪达唑仑、未结合的和葡萄糖醛酸化的1-羟基咪达唑仑的药代动力学及清除情况。通过高效液相色谱法（HPLC）对持续输注期间及输注结束后采集的血样中的血浆咪达唑仑及其代谢物进行评估。采集动脉和静脉血路及超滤液的额外样本以计算筛滤系数和超滤清除率。咪达唑仑的消除半衰期为7.6至22.8小时。超滤清除率在0.13至4.7 ml/分钟之间，约占总清除率的11%。筛滤系数范围为0.006至0.26，平均清除分数为0.2%。1-羟基咪达唑仑葡萄糖醛酸通过持续血液透析被清除（筛滤系数为0.36至0.63），超滤清除率为7.8至12.0 ml/分钟。这些初步结果表明，咪达唑仑清除效率不高，约一半的1-羟基咪达唑仑葡萄糖醛酸通过透析被清除。
