There are no pharmacokinetic data in children on
terizidone, a
pro-drug of
cycloserine and a World Health Organization (WHO)-recommended group B
drug for
rifampicin-resistant
tuberculosis (RR-TB) treatment. We collected pharmacokinetic data in children <15 years routinely receiving 15-20 mg/kg of daily
terizidone for RR-TB treatment. We developed a population pharmacokinetic model of
cycloserine assuming a 2-to-1 molecular ratio between
terizidone and
cycloserine. We included 107 children with median (interquartile range) age and weight of 3.33 (1.55, 5.07) years and 13.0 (10.1, 17.0) kg, respectively. The pharmacokinetics of
cycloserine was described with a one-compartment model with first-order elimination and parallel transit compartment absorption. Allometric scaling using fat-free mass best accounted for the effect of body size, and clearance displayed maturation with age. The clearance in a typical 13 kg child was estimated at 0.474 L/h. The mean absorption transit time when capsules were opened and administered as
powder was significantly faster compared to when capsules were swallowed whole (10.1 vs 72.6 min) but with no effect on bioavailability. Lower bioavailability (-16%) was observed in children with weight-for-age z-score below -2. Compared to adults given 500 mg daily
terizidone, 2022 WHO-recommended pediatric doses result in lower exposures in weight bands 3-10 kg and 36-46 kg. We developed a population pharmacokinetic model in children for
cycloserine dosed as
terizidone and characterized the effects of body size, age, formulation manipulation, and underweight-for-age. With current
terizidone dosing, pediatric
cycloserine exposures are lower than adult values for several weight groups. New optimized dosing is suggested for prospective evaluation.