Pharmacokinetics of Midazolam in Critically Ill Pediatric Patients

Overview

Journal Eur J Drug Metab Pharmacokinet

Date 2001 Jun 26

PMID 11420893

Citations 4

Authors

M C Nahara

J McMorrow

P R Jones

D Anglin

R Rosenberg

Affiliations

Soon will be listed here.

Abstract

Midazolam is frequently used to produce sedation in critically ill pediatric patients. We studied the pharmacokinetics of midazolam in 22 patients (age 8 days to 16 years). The intravenous infusion rate to produce sedation ranged from 49-385 mcg/kg/hr. The blood samples were obtained at steady-state and midazolam was measured by gas chromatography with electron capture. The steady-state plasma concentrations of midazolam ranged from 49-385 ng/mL. The total clearance, apparent volume of distribution, and elimination half-life ranged from 0.1-3.1 L/kg/hr, 0.2-3.5 L/kg, and 0.3-10.9 hours, respectively. The marked interpatient variability in pharmacokinetics explains in part, the substantial variation in dosage requirements of midazolam to produce sedation in critically ill pediatric patients.

Citing Articles

The Oral Bioavailability and Metabolism of Midazolam in Stable Critically Ill Children: A Pharmacokinetic Microtracing Study.

van Groen B, Krekels E, Mooij M, van Duijn E, Vaes W, Windhorst A Clin Pharmacol Ther. 2020; 109(1):140-149.

PMID: 32403162 PMC: 7818442. DOI: 10.1002/cpt.1890.

Predicting CYP3A-mediated midazolam metabolism in critically ill neonates, infants, children and adults with inflammation and organ failure.

Brussee J, Vet N, Krekels E, Valkenburg A, Jacqz-Aigrain E, van Gerven J Br J Clin Pharmacol. 2017; 84(2):358-368.

PMID: 29072785 PMC: 5777436. DOI: 10.1111/bcp.13459.

Scaling clearance in paediatric pharmacokinetics: All models are wrong, which are useful?.

Germovsek E, Barker C, Sharland M, Standing J Br J Clin Pharmacol. 2016; 83(4):777-790.

PMID: 27767204 PMC: 5346879. DOI: 10.1111/bcp.13160.

Inter-individual variation in midazolam clearance in children.

Altamimi M, Sammons H, Choonara I Arch Dis Child. 2014; 100(1):95-100.

PMID: 25281734 PMC: 4283666. DOI: 10.1136/archdischild-2013-305720.

References

Jones R, Chan K, Roulson C, Brown A, Smith I, Mya G . Pharmacokinetics of flumazenil and midazolam. Br J Anaesth. 1993; 70(3):286-92. DOI: 10.1093/bja/70.3.286. View

Boulieu R, Lehmann B, Salord F, Fisher C, Morlet D . Pharmacokinetics of midazolam and its main metabolite 1-hydroxymidazolam in intensive care patients. Eur J Drug Metab Pharmacokinet. 1998; 23(2):255-8. DOI: 10.1007/BF03189348. View

Hartwig S, Roth B, Theisohn M . Clinical experience with continuous intravenous sedation using midazolam and fentanyl in the paediatric intensive care unit. Eur J Pediatr. 1991; 150(11):784-8. DOI: 10.1007/BF02026712. View

Lee T, Charles B, Harte G, Gray P, Steer P, Flenady V . Population pharmacokinetic modeling in very premature infants receiving midazolam during mechanical ventilation: midazolam neonatal pharmacokinetics. Anesthesiology. 1999; 90(2):451-7. DOI: 10.1097/00000542-199902000-00020. View

Blumer J . Clinical pharmacology of midazolam in infants and children. Clin Pharmacokinet. 1998; 35(1):37-47. DOI: 10.2165/00003088-199835010-00003. View

Allonen H, Ziegler G, Klotz U . Midazolam kinetics. Clin Pharmacol Ther. 1981; 30(5):653-61. DOI: 10.1038/clpt.1981.217. View

Bach V, Carl P, Ravlo O, Crawford M, Jensen A, Mikkelsen B . A randomized comparison between midazolam and thiopental for elective cesarean section anesthesia: III. Placental transfer and elimination in neonates. Anesth Analg. 1989; 68(3):238-42. View

Tolia V, Brennan S, Aravind M, Kauffman R . Pharmacokinetic and pharmacodynamic study of midazolam in children during esophagogastroduodenoscopy. J Pediatr. 1991; 119(3):467-71. DOI: 10.1016/s0022-3476(05)82066-9. View

Burtin P, Jacqz-Aigrain E, Girard P, Lenclen R, Magny J, Betremieux P . Population pharmacokinetics of midazolam in neonates. Clin Pharmacol Ther. 1994; 56(6 Pt 1):615-25. DOI: 10.1038/clpt.1994.186. View

10.

Asokumar B, Cheng D, Chung F, Peniston C, Sandler A, Varin F . Pharmacokinetics of doxacurium during normothermic and hypothermic cardiopulmonary bypass surgery. Can J Anaesth. 1998; 45(6):515-20. DOI: 10.1007/BF03012700. View

11.

Mathews H, Carson I, Lyons S, Orr I, Collier P, Howard P . A pharmacokinetic study of midazolam in paediatric patients undergoing cardiac surgery. Br J Anaesth. 1988; 61(3):302-7. DOI: 10.1093/bja/61.3.302. View

12.

Hughes J, Gill A, Mulhearn H, Powell E, Choonara I . Steady-state plasma concentrations of midazolam in critically ill infants and children. Ann Pharmacother. 1996; 30(1):27-30. DOI: 10.1177/106002809603000104. View

13.

Jacqz-Aigrain E, Daoud P, Burtin P, Maherzi S, Beaufils F . Pharmacokinetics of midazolam during continuous infusion in critically ill neonates. Eur J Clin Pharmacol. 1992; 42(3):329-32. DOI: 10.1007/BF00266357. View

14.

Jacqz-Aigrain E, Wood C, Robieux I . Pharmacokinetics of midazolam in critically ill neonates. Eur J Clin Pharmacol. 1990; 39(2):191-2. DOI: 10.1007/BF00280059. View

15.

Rey E, Delaunay L, Pons G, Murat I, Richard M, Olive G . Pharmacokinetics of midazolam in children: comparative study of intranasal and intravenous administration. Eur J Clin Pharmacol. 1991; 41(4):355-7. DOI: 10.1007/BF00314967. View

16.

Payne K, Mattheyse F, Liebenberg D, Dawes T . The pharmacokinetics of midazolam in paediatric patients. Eur J Clin Pharmacol. 1989; 37(3):267-72. DOI: 10.1007/BF00679782. View

17.

Kraus G, Gruber R, Knoll R, Danner U . [Pharmacokinetic studies following intravenous and rectal administration of midazolam in children]. Anaesthesist. 1989; 38(12):658-63. View

18.

Vasiliades J, Sahawneh T . Midazolam determination by gas chromatography, liquid chromatography and gas chromatography--mass spectrometry. J Chromatogr. 1982; 228:195-203. DOI: 10.1016/s0378-4347(00)80432-6. View