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.
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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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