Trimethoprim/Sulfamethoxazole Kinetics in Children with Biliary Atresia

Lares‐Asseff, Ismael; Villegas, Fernando; Pérez-Guillé, Gabriela; Toledo, Alicia; Camacho, Angélica; López, María del Carmen López

doi:10.1177/106002809402800323

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“…This is the first PopPK analysis of TMP-SMX administered by the enteral route in infants and children with dose-exposure simulations to support dosing recommendations for various indications. Similar to a published TMP and SMX PK model developed using data for adults, one-compartment models best characterized the data for both components (10)(11)(12)(13)(14). Population estimates for the TMP and SMX K a were similar to values previously reported in adults (1.6 h Ϫ1 and 0.4 h Ϫ1 , respectively) (10, 15).…”

Section: Discussionsupporting

confidence: 71%

Population Pharmacokinetics of Trimethoprim-Sulfamethoxazole in Infants and Children

Autmizguine

Melloni

Hornik

et al. 2018

Antimicrob Agents Chemother

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Trimethoprim (TMP)-sulfamethoxazole (SMX) is used to treat various types of infections, including community-acquired methicillin-resistant (CA-MRSA) and infections in children. Pharmacokinetic (PK) data for infants and children are limited, and the optimal dosing is not known. We performed a multicenter, prospective PK study of TMP-SMX in infants and children. Separate population PK models were developed for TMP and SMX administered by the enteral route using nonlinear mixed-effects modeling. Optimal dosing was determined on the basis of the matching adult TMP exposure and attainment of the surrogate pharmacodynamic (PD) target for efficacy, a free TMP concentration above the MIC over 50% of the dosing interval. Data for a total of 153 subjects (240 samples for PK analysis) with a median postnatal age of 8 years (range, 0.1 to 20 years) contributed to the analysis for both drugs. A one-compartment model with first-order absorption and elimination characterized the TMP and SMX PK data well. Weight was included in the base model for clearance (CL/) and volume of distribution (/). Both TMP and SMX CL/ increased with age. In addition, TMP and SMX CL/ were inversely related to the serum creatinine and albumin concentrations, respectively. The exposure achieved in children after oral administration of TMP-SMX at 8/40 mg/kg of body weight/day divided into administration every 12 h matched the exposure achieved in adults after administration of TMP-SMX at 320/1,600 mg/day divided into administration every 12 h and achieved the PD target for bacteria with an MIC of 0.5 mg/liter in >90% of infants and children. The exposure achieved in children after oral administration of TMP-SMX at 12/60 and 15/75 mg/kg/day divided into administration every 12 h matched the exposure achieved in adults after administration of TMP-SMX at 640/3,200 mg/day divided into administration every 12 h in subjects 6 to <21 years and 0 to <6 years of age, respectively, and was optimal for bacteria with an MIC of up to 1 mg/liter.

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