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Dosing of ceftriaxone and metronidazole for children with severe acute malnutrition.

Standing, JF; Ongas, MO; Ogwang, C; Kagwanja, N; Murunga, S; Mwaringa, S; Ali, R; ... FLACSAM-PK Study Group; + view all (2018) Dosing of ceftriaxone and metronidazole for children with severe acute malnutrition. Clinical Pharmacology & Therapeutics , 104 (6) pp. 1165-1174. 10.1002/cpt.1078. Green open access

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Abstract

Infants and young children with severe acute malnutrition (SAM) are treated with empiric broad-spectrum antimicrobials. Parenteral ceftriaxone is currently a second-line agent for invasive infection. Oral metronidazole principally targets small intestinal bacterial overgrowth. Children with SAM may have altered drug absorption, distribution, metabolism and elimination. Population pharmacokinetics of ceftriaxone and metronidazole were studied, with the aim of recommending optimal dosing. Eighty-one patients with SAM (aged 2-45 months) provided 234 post-dose pharmacokinetic samples for total ceftriaxone, metronidazole and hydroxymetronidazole. Ceftriaxone protein binding was also measured in 190 of these samples. A 3-compartment model adequately described free ceftriaxone, with a Michaelis-Menten model for concentration and albumin dependent protein binding. A 1-compartment model was used for both metronidazole and hydroxymetronidazole, with only 1% of hydroxymetronidazole predicted to be formed during first-pass. Simulations showed 80 mg/kg once daily of ceftriaxone and 12.5 mg/kg twice daily of metronidazole were sufficient to reach therapeutic targets. This article is protected by copyright. All rights reserved.

Type: Article
Title: Dosing of ceftriaxone and metronidazole for children with severe acute malnutrition.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/cpt.1078
Publisher version: https://doi.org/10.1002/cpt.1078
Language: English
Additional information: © 2018 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: Ceftriaxone, metronidazole, pharmacokinetics, severe acute malnutrition
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10047193
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