Pharmacokinetics and clinical efficacy of midazolam in children with severe malaria and convulsions

Muchohi, S. N., Kokwaro, G. O., Ogutu, B. R., Edwards, Geoffrey, Ward, Stephen ORCID: https://orcid.org/0000-0003-2331-3192 and Newton, C. R. J. C. (2008) 'Pharmacokinetics and clinical efficacy of midazolam in children with severe malaria and convulsions'. British Journal of Clinical Pharmacology, Vol 66, Issue 4, pp. 529-538.

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Abstract

Midazolam (MDZ), a water-soluble benzodiazepine, can be administered via several routes, including intravenously (IV), intramuscularly (IM) and buccal routes to terminate convulsions. It may be a suitable alternative to diazepam to stop convulsions in children with severe malaria, especially at peripheral healthcare facilities. The pharmacokinetics of MDZ have not been described in African children, in whom factors such as the aetiology and nutritional status may influence the pharmacokinetics.
Administration of MDZ (IV, IM, or buccal) at the currently recommended dose (0.3 mg kg−1) resulted in rapid achievement of median maximum plasma concentrations of MDZ within the range 64–616 ng ml−1, with few clinically significant cardio-respiratory effects. A single dose of MDZ rapidly terminated (within 10 min) seizures in all (100%), 9/12 (75%) and 5/8 (63%) children following IV, IM and buccal administration, respectively. Although IM and buccal MDZ may be the preferred treatment for children in the pre-hospital settings the efficacy appears to be poorer.

Item Type:	Article
Uncontrolled Keywords:	children convulsions malaria midazolam pharmacokinetics severe falciparum-malaria childhood cerebral malaria critically-ill patients status epilepticus buccal midazolam rectal diazepam population pharmacokinetics prolonged seizures african children intramuscular midazolam
Subjects:	WS Pediatrics > Diseases of Children and Adolescents > By System > WS 340 Nervous system QX Parasitology > Protozoa > QX 135 Plasmodia WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria QV Pharmacology > QV 38 Drug action.
Faculty: Department:	Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI):	https://doi.org/10.1111/j.1365-2125.2008.03239.x
Depositing User:	Mary Creegan
Date Deposited:	19 Jul 2010 09:37
Last Modified:	17 Jul 2020 10:56
URI:	https://archive.lstmed.ac.uk/id/eprint/871

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