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Pharmacokinetics of praziquantel in Schistosoma mansoni and Schistosoma haematobium infected school- and preschool- aged children

Kovač, Jana and Meister, Isabel and Neodo, Anna and Panic, Gordana and Coulibaly, Jean T. and Falcoz, Christine and Keiser, Jennifer. (2018) Pharmacokinetics of praziquantel in Schistosoma mansoni and Schistosoma haematobium infected school- and preschool- aged children. Antimicrobial agents and chemotherapy, 62 (8). e02253-17.

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Official URL: https://edoc.unibas.ch/65199/

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Abstract

There is a growing consensus to include preschool-aged children in preventive chemotherapy programs with praziquantel to improve schistosomiasis control. However, pharmacokinetic data, crucial to establish a safe and effective dose for this age group, are sparse. The objective of this study was to establish and compare the pharmacokinetic parameters of praziquantel in preschool- and school-aged children with schistosomiasis. Two pharmacokinetic trials in school- and preschool-aged children infected with; Schistosoma mansoni; or; S. haematobium; were conducted in Côte d'Ivoire. Dried blood spot samples were taken from 492 children at 10 time points following a single oral dose of 20, 40, or 60 mg/kg of body weight of praziquantel and analyzed using liquid chromatography-mass spectrometry. Noncompartmental analysis (NCA) was performed to obtain the pharmacokinetic parameters of; R; -praziquantel (RPZQ),; S; -praziquantel (SPZQ), and; R-trans; -4-hydroxy-praziquantel. No significant differences in pharmacokinetic parameters between species-specific infections were observed. While pharmacokinetic parameters differed significantly between age groups for; S. mansoni; , this trend was not observed with; S. haematobium; Neither the area under the curve (AUC) nor the maximal blood concentration (; C; max; ) presented clear dose proportionality for R- and SPZQ. Logistic regression indicated a relationship between the RPZQ AUC and; C; max; and the probability of cure. Praziquantel is subject to complex metabolic processes following erratic absorption. While the results of NCA are a very informative base for a better understanding of the drug, a more targeted approach in the form of population modeling is needed to quantify the factors influencing metabolic processes and draw conclusions.
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:Kovac, Jana and Meister, Isabel and Panic, Gordana 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
Identification Number:
Last Modified:11 Sep 2018 11:52
Deposited On:11 Sep 2018 11:52

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