Pharmacometric Analysis of Tribendimidine Monotherapy and Combination Therapies To Achieve High Cure Rates in Patients with Hookworm Infections.
combination chemotherapy
combination therapy
deacetylated amidantel
drug-drug interaction
hookworm
ivermectin
oxantel pamoate
pharmacokinetics
soil-transmitted helminths
tribendimidine
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:
20 01 2021
20 01 2021
Historique:
received:
14
04
2020
accepted:
27
09
2020
pubmed:
4
11
2020
medline:
22
6
2021
entrez:
3
11
2020
Statut:
epublish
Résumé
In the treatment of hookworm infections, pharmacotherapy has been only moderately successful and drug resistance is a threat. Therefore, novel treatment options including combination therapies should be considered, in which tribendimidine could play a role. Our aims were to (i) characterize the pharmacokinetics of tribendimidine's metabolites in adolescents receiving tribendimidine monotherapy or in combination with ivermectin or oxantel pamoate, (ii) evaluate possible drug-drug interactions (DDI), (iii) link exposure to response, and (iv) identify a treatment strategy associated with high efficacy, i.e., >90% cure rates (CRs), utilizing model-based simulations. A population pharmacokinetic model was developed for tribendimidine's primary and secondary metabolites, dADT and adADT, in 54 hookworm-positive adolescents, with combination therapy evaluated as a possible covariate. Subsequently, an exposure-response analysis was performed utilizing CRs as response markers. Simulations were performed to identify a treatment strategy to achieve >90% CRs. A two-compartmental model best described metabolite disposition. No pharmacokinetic DDI was identified with ivermectin or oxantel pamoate. All participants receiving tribendimidine plus ivermectin were cured. For the monotherapy arm and the arm including the combination with oxantel pamoate,
Identifiants
pubmed: 33139276
pii: AAC.00714-20
doi: 10.1128/AAC.00714-20
pmc: PMC7849000
pii:
doi:
Substances chimiques
Anthelmintics
0
Phenylenediamines
0
tribendimidine
115103-15-6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2021 American Society for Microbiology.
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