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

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. Mida...

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Main Author: Gian Maria Pacifici
Format: Article
Language:English
Published: Wiley 2014-01-01
Series:International Journal of Pediatrics
Online Access:http://dx.doi.org/10.1155/2014/309342
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author Gian Maria Pacifici
author_facet Gian Maria Pacifici
author_sort Gian Maria Pacifici
collection DOAJ
description 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.
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spelling doaj-art-7c19eb50f831416a90056d6f95f522032025-08-20T02:06:54ZengWileyInternational Journal of Pediatrics1687-97401687-97592014-01-01201410.1155/2014/309342309342Clinical Pharmacology of Midazolam in Neonates and Children: Effect of Disease—A ReviewGian Maria Pacifici0Section of Pharmacology, Department of Translational Research and New Technologies in Medicine and Surgery, Medical School, University of Pisa, 56126 Pisa, ItalyMidazolam 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.http://dx.doi.org/10.1155/2014/309342
spellingShingle Gian Maria Pacifici
Clinical Pharmacology of Midazolam in Neonates and Children: Effect of Disease—A Review
International Journal of Pediatrics
title Clinical Pharmacology of Midazolam in Neonates and Children: Effect of Disease—A Review
title_full Clinical Pharmacology of Midazolam in Neonates and Children: Effect of Disease—A Review
title_fullStr Clinical Pharmacology of Midazolam in Neonates and Children: Effect of Disease—A Review
title_full_unstemmed Clinical Pharmacology of Midazolam in Neonates and Children: Effect of Disease—A Review
title_short Clinical Pharmacology of Midazolam in Neonates and Children: Effect of Disease—A Review
title_sort clinical pharmacology of midazolam in neonates and children effect of disease a review
url http://dx.doi.org/10.1155/2014/309342
work_keys_str_mv AT gianmariapacifici clinicalpharmacologyofmidazolaminneonatesandchildreneffectofdiseaseareview