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Pharmacokinetics of a pediatric tribendimidine dose-finding study to treat hookworm infection in African children

Hiroshige, Noemi and Coulibaly, Jean and Huwyler, Jörg and Bonate, Peter L. and Keiser, Jennifer. (2018) Pharmacokinetics of a pediatric tribendimidine dose-finding study to treat hookworm infection in African children. Antimicrobial agents and chemotherapy, 62 (9). e00959-18.

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Official URL: https://edoc.unibas.ch/65685/

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Abstract

Tribendimidine is a broad-spectrum anthelminthic available in China, which is currently being pursued for U.S. Food and Drug Administration approval for soil-transmitted helminth infections. Pharmacokinetic (PK) studies with tribendimidine in children, the main target group for treatment programs, have not been conducted to date. In the framework of a dose-ranging study in hookworm-infected school-aged children in Côte d'Ivoire, children were treated with either 100, 200, or 400 mg tribendimidine. Dried blood spot samples were collected up to 22 h after treatment. The active metabolite, deacetylated amidantel (dADT) and its metabolite acylated dADT (adADT) were quantified using liquid chromatography tandem mass spectrometry. PK parameters were calculated using a noncompartmental model, and univariate logistic regression was applied using maximal blood concentrations (; C; max; ) and area under the blood concentration-time curve for 0 to 22 h (AUC; 0-22; ) as predictors of drug efficacy. Dried blood spot samples of 101 children were analyzed. We observed a less than proportional and proportional exposure in dADT's median; C; max; and AUC; 0-22; , respectively, following administration of 100 mg (; C; max; = 853 ng/ml; AUC; 0-22; = 3,019 h · ng/ml) and 400 mg (; C; max; = 2,275 ng/ml; AUC; 0-22; = 12,530 h · ng/ml) tribendimidine. There were large, dose-independent variations in the time to; C; max; (; T; max; ) and ratios of dADT to adADT. We did not detect an influence of; C; max; or AUC; 0-22; of dADT or adADT on drug efficacy or adverse events. Since our study population was bearing hookworm infection of mainly low intensity, additional studies with heavy intensity infections might be required to confirm this observation.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Helminth Drug Development (Keiser)
UniBasel Contributors:Hiroshige, Noemi and Coulibaly, Jean and Keiser, Jennifer
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Society for Microbiology
ISSN:0066-4804
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:16 Oct 2018 16:10
Deposited On:16 Oct 2018 16:06

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