Population pharmacokinetics of benznidazole in neonates, infants and children using a new pediatric formulation.

BackgroundThere is a major need for information on pharmacokinetics (PK) of benznidazole (BNZ) in children with Chagas disease (CD). We conducted a multicentre population PK, safety and efficacy study in children, infants and neonates with CD treated with BNZ (formulated in 100 mg tablets or 12.5 mg dispersible tablets, developed by the pharmaceutical company LAFEPE, in a collaboration with DNDi).Methods81 children 0-12 years old were enrolled at 5 pediatric centers in Argentina. Diagnosis of T. cruzi infection was confirmed by direct microscopic examination, or at least two positive conventional serological tests. Subject enrolment was stratified by age: newborns to 2 years (minimum of 10 newborns) and >2-12 years. BNZ 7.5 mg/kg/d was administered in two daily doses for 60 days. Five blood samples per child were obtained at random times within pre-defined time windows at Day 0 at 2-5 h post-dose; during steady state, one sample at Day 7 and at Day 30; and two samples at 12-24 h after final BNZ dose at Day 60. The primary efficacy endpoint was parasitological clearance by qualitative PCR at the end of treatment.ResultsForty-one (51%) patients were under 2 years of age (including 14 newborns ConclusionWe observed lower BNZ plasma concentrations in infants and children than those previously reported in adults treated with comparable mg/kg doses. Despite these lower concentrations, pediatric treatment was well tolerated and universally effective, with a high response rate and infrequent, mild AEs.Trial registrationRegistered in clinicaltrials.gov #NCT01549236