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International Journal of Pediatrics
Volume 2014 (2014), Article ID 309342, 20 pages
http://dx.doi.org/10.1155/2014/309342
Review Article

Clinical Pharmacology of Midazolam in Neonates and Children: Effect of Disease—A Review

Section of Pharmacology, Department of Translational Research and New Technologies in Medicine and Surgery, Medical School, University of Pisa, 56126 Pisa, Italy

Received 9 November 2013; Accepted 26 December 2013; Published 18 February 2014

Academic Editor: Steven M. Donn

Copyright © 2014 Gian Maria Pacifici. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Midazolam is a benzodiazepine with rapid onset of action and short duration of effect. In healthy neonates the half-life (t1/2) and the clearance (Cl) are 3.3-fold longer and 3.7-fold smaller, respectively, than in adults. The volume of distribution (Vd) is 1.1 L/kg both in neonates and adults. Midazolam is hydroxylated by CYP3A4 and CYP3A5; the activities of these enzymes surge in the liver in the first weeks of life and thus the metabolic rate of midazolam is lower in neonates than in adults. Midazolam acts as a sedative, as an antiepileptic, for those infants who are refractory to standard antiepileptic therapy, and as an anaesthetic. Information of midazolam as an anaesthetic in infants are very little. Midazolam is usually administered intravenously; when minimal sedation is required, intranasal administration of midazolam is employed. Disease affects the pharmacokinetics of midazolam in neonates; multiple organ failure reduces the Cl of midazolam and mechanical ventilation prolongs the t1/2 of this drug. ECMO therapy increases t1/2, Cl, and Vd of midazolam several times. The adverse effects of midazolam in neonates are scarce: pain, tenderness, and thrombophlebitis may occur. Respiratory depression and hypotension appear in a limited percentage of infants following intravenous infusion of midazolam. In conclusion, midazolam is a safe and effective drug which is employed as a sedative, as antiepileptic agent, for infants who are refractory to standard antiepileptic therapy, and as an anaesthetic.