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.