Optimal regimens of praziquantel for schistosomiasis in young children

Praziquantel (PZQ) is the drug of choice for control and treatment of schistosomiasis. Pharmacokinetic (PK) data for establishing a safe and effective PZQ dose in preschool-aged children are limited. We characterized PZQ pharmacokinetics in children aged 1–4 years with intestinal schistosomiasis. PZQ was administered at either 40 mg/kg or 80 mg/kg (split into two doses of 40 mg/kg, 3 h apart), and plasma concentrations were quantified. These data were pooled with pre-existing PK data from children aged 3–8 years, who received PZQ 40 mg/kg or 60 mg/kg. A population PK model was fitted to the pooled data, and individual drug exposure was estimated. Pharmacodynamic outcomes were egg reduction rate, and both parasitological and antigenic cure at 4 weeks post-treatment. The relationship between PZQ exposure and cure was established using regression analysis. Monte Carlo simulations were performed to assess the adequacy of weight-based PZQ dosing. A two-compartment model, with first-order absorption and elimination, best described PZQ disposition. Total body weight was allowed to influence clearance and the central compartment volume, with fixed allometric exponents 0.75 and 1, respectively. Simulations indicated that both weight-banded fixed-dose regimens and individual weight-based dosing achieved comparable drug exposures. The area under the concentration-time curve (AUC _0–24 ) of the total drug was a strong predictor of parasitological cure. PZQ 80 mg/kg achieved parasitological cure rates >85% but may still be insufficient for complete worm elimination, as demonstrated by the lower rate (69.5%) of antigen clearance. Further optimization of anti-schistosomiasis treatments may be required to achieve complete worm elimination in mass treatment programs.