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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\/<jats:italic>F<\/jats:italic>) and volume of distribution (<jats:italic>V<\/jats:italic>\/<jats:italic>F<\/jats:italic>). Both TMP and SMX CL\/<jats:italic>F<\/jats:italic>increased with age. In addition, TMP and SMX CL\/<jats:italic>F<\/jats:italic>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 &gt;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 &lt;21 years and 0 to &lt;6 years of age, respectively, and was optimal for bacteria with an MIC of up to 1 mg\/liter.<\/jats:p>","DOI":"10.1128\/aac.01813-17","type":"journal-article","created":{"date-parts":[[2017,10,30]],"date-time":"2017-10-30T15:50:27Z","timestamp":1509378627000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":24,"title":["Population Pharmacokinetics of Trimethoprim-Sulfamethoxazole in Infants and Children"],"prefix":"10.1128","volume":"62","author":[{"given":"Julie","family":"Autmizguine","sequence":"first","affiliation":[{"name":"Research Center, CHU Sainte-Justine, and Department of Pharmacology and Physiology, Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Melloni","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph P.","family":"Hornik","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Dallefeld","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barrie","family":"Harper","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram","family":"Yogev","sequence":"additional","affiliation":[{"name":"Ann and Robert H. 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