Population Pharmacokinetics of Mefloquine Intermittent Preventive Treatment for Malaria in Pregnancy in Gabon.
Plasmodium falciparum
malaria
mefloquine
population pharmacokinetics
pregnancy
Journal
Antimicrobial agents and chemotherapy
ISSN: 1098-6596
Titre abrégé: Antimicrob Agents Chemother
Pays: United States
ID NLM: 0315061
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
31
05
2018
accepted:
08
11
2018
pubmed:
21
11
2018
medline:
28
1
2020
entrez:
21
11
2018
Statut:
epublish
Résumé
Mefloquine was evaluated as an alternative for intermittent preventive treatment of malaria in pregnancy (IPTp) due to increasing resistance against the first-line drug sulfadoxine-pyrimethamine (SP). This study determined the pharmacokinetic characteristics of the mefloquine stereoisomers and the metabolite carboxymefloquine (CMQ) when given as IPTp in pregnant women. Also, the relationship between plasma concentrations of the three analytes and cord samples was evaluated, and potential covariates influencing the pharmacokinetic properties were assessed. A population pharmacokinetic analysis was performed with 264 pregnant women from a randomized controlled trial evaluating a single and a split-dose regimen of two 15-mg/kg mefloquine doses at least 1 month apart versus SP-IPTp. Both enantiomers of mefloquine and its carboxy-metabolite (CMQ), measured in plasma and cord samples, were applied for pharmacokinetic modelling using NONMEM 7.3. Both enantiomers and CMQ were described simultaneously by two-compartment models. In the split-dose group, mefloquine bioavailability was significantly increased by 5%. CMQ induced its own metabolism significantly. Maternal and cord blood concentrations were significantly correlated (
Identifiants
pubmed: 30455233
pii: AAC.01113-18
doi: 10.1128/AAC.01113-18
pmc: PMC6355560
pii:
doi:
Substances chimiques
Antimalarials
0
Drug Combinations
0
Ro 21-5104
35853-50-0
fanasil, pyrimethamine drug combination
37338-39-9
Sulfadoxine
88463U4SM5
Mefloquine
TML814419R
Pyrimethamine
Z3614QOX8W
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2019 American Society for Microbiology.
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