Pharmacokinetics of Praziquantel in Schistosoma mansoni- and Schistosoma haematobium-Infected School- and Preschool-Aged Children.

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.
(Copyright © 2018 American Society for Microbiology.)