Rifampicin-resistant tuberculosis (RR-TB) therapy choices for children were limited, and para-aminosalicylic acid (PAS) remained an important component of treatment regimens. PAS’s ability to prevent companion drug resistance was dose-dependent, and at higher doses. The best way to give PAS to children was through delayed-release granule preparations, the most common. The pharmacokinetics of PAS in children undergoing routine RR-TB medication was studied using a population pharmacokinetic model. Current World Health Organization (WHO) weight-band dosages were compared to the adult pharmacokinetic target of 50 to 100 mg/liter for peak concentrations in model-based simulations. The median (range) age and weight of the 27 children included were 3.87 (0.58 to 13.7) years, and 13.3 (7.15 to 30.5) kg, respectively; 4 (14.8%) were HIV positive. With first-order elimination and transit compartment absorption, PAS followed one-compartment kinetics. A 13-kg child’s average clearance was 9.79 liters per hour. The sole patient receiving efavirenz had increased PAS clearance in both pharmacokinetic profiles. There was no influence on renal function, sex, ethnicity, nutritional status, HIV status, antiretrovirals (lamivudine, abacavir, and lopinavir-ritonavir), or RR-TB medications on HIV status, antiretrovirals (lamivudine, abacavir, and Only the upper WHO dose range of 300 mg/kg once daily was used in simulations to obtain goal concentrations. For the slow-release PAS formulation, a transit compartment appropriately describes absorption. To maximize treatment, children should be dosed at the higher end of the current WHO-recommended PAS dose range and in a once-daily dose.
Source:journals.asm.org/doi/10.1128/aac.02264-21
