Population pharmacokinetics of trimethoprim- sulfamethoxazole in infants and children
Date
2018Journal
Antimicrobial Agents and ChemotherapyPublisher
American Society for MicrobiologyType
Article
Metadata
Show full item recordAbstract
Trimethoprim (TMP)-sulfamethoxazole (SMX) is used to treat various types of infections, including community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) and Pneumocystis jirovecii 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/F) and volume of distribution (V/F). Both TMP and SMX CL/F increased with age. In addition, TMP and SMX CL/F 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. Copyright Copyright 2017 American Society for Microbiology. All Rights Reserved.Sponsors
This work was funded under National Institute of Child Health and Human Development (NICHD) contract HHSN275201000003I for the Pediatric Trials Network (PI, Danny Benjamin).Keyword
ChildrenInfants
Methicillin-resistant Staphylococcus aureus
Pharmacokinetics
Sulfamethoxazole
Trimethoprim
Identifier to cite or link to this item
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85039793051&doi=10.1128%2fAAC.01813-17&partnerID=40&md5=93a9ae34f315898456803c5d83f30dbc; http://hdl.handle.net/10713/9695ae974a485f413a2113503eed53cd6c53
10.1128/AAC.01813-17
Scopus Count
Collections
Related articles
- External Evaluation of Two Pediatric Population Pharmacokinetics Models of Oral Trimethoprim and Sulfamethoxazole.
- Authors: Wu YSS, Cohen-Wolkowiez M, Hornik CP, Gerhart JG, Autmizguine J, Cobbaert M, Gonzalez D, Best Pharmaceuticals for Children Act—Pediatric Trials Network Steering Committee.
- Issue date: 2021 Jun 17
- Physiologically Based Pharmacokinetic Modeling for Trimethoprim and Sulfamethoxazole in Children.
- Authors: Thompson EJ, Wu H, Maharaj A, Edginton AN, Balevic SJ, Cobbaert M, Cunningham AP, Hornik CP, Cohen-Wolkowiez M
- Issue date: 2019 Jul
- Treatment of methicillin-resistant Staphylococcus aureus infections with a minimal inhibitory concentration of 2 μg/mL to vancomycin: old (trimethoprim/sulfamethoxazole) versus new (daptomycin or linezolid) agents.
- Authors: Campbell ML, Marchaim D, Pogue JM, Sunkara B, Bheemreddy S, Bathina P, Pulluru H, Chugh N, Wilson MN, Moshos J, Ku K, Hayakawa K, Martin ET, Lephart PR, Rybak MJ, Kaye KS
- Issue date: 2012 Dec
- High incidence of antimicrobial resistant organisms including extended spectrum beta-lactamase producing Enterobacteriaceae and methicillin-resistant Staphylococcus aureus in nasopharyngeal and blood isolates of HIV-infected children from Cape Town, South Africa.
- Authors: Cotton MF, Wasserman E, Smit J, Whitelaw A, Zar HJ
- Issue date: 2008 Apr 1
- Suboptimal cotrimoxazole prophylactic concentrations in HIV-infected children according to the WHO guidelines.
- Authors: Pressiat C, Mea-Assande V, Yonaba C, Treluyer JM, Dahourou DL, Amorissani-Folquet M, Blanche S, Eboua F, Ye D, Lui G, Malateste K, Zheng Y, Leroy V, Hirt D, MONOD Study Group.
- Issue date: 2017 Dec