Midazolam disposition in patients undergoing continuous venovenous hemodialysis
M Bolon1, O Bastien, C Flamens
1Université Claude Bernard Lyon 1, Institut des Sciences Pharmaceutiques et Biologiques, Département de Pharmacie clinque, de Pharmacocinétique et d'Evaluation du Médicament, France.
Abstract:
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.
Related Concept Videos
Sedatives and Hypnotics Drugs: Benzodiazepines
Benzodiazepines work by enhancing the effects of the inhibitory neurotransmitter GABA. They bind to the GABAA receptor, increasing its affinity for GABA, which opens chloride...
Drug Accumulation During Multiple Dosing: Intermittent IV Infusions
Drug Dosing in Renal Diseases: Dose Adjustments Based on Drug Clearance and Elimination Rate Constant
Continuous Renal Replacement Therapy
Hemodialysis II: Procedure and Complications
Hemodialysis III: Nursing Management


