Population pharmacokinetics of pyrimethamine and sulfadoxine in children treated for congenital toxoplasmosis

Antimicrobial Agents and Chemotherapy
Stéphane CorvaisierF Peyron

Abstract

The population pharmacokinetics of pyrimethamine (PYR) and sulfadoxine (SDX) for a group of 32 children with congenital toxoplasmosis was investigated by nonparametric modeling analysis. A one-compartment model was used as the structural model, and individual pharmacokinetic parameters were estimated by Bayesian modeling. PYR (1.25 mg/kg of body weight) and SDX (25 mg/kg) were administered orally every 10 days for 1 year, with adjustment of the dose to body weight every 3 months. Drug concentrations were measured by high-performance liquid chromatography. A total of 101 measurements in serum were available for both drugs. Mean absorption rate constants, volumes of distribution, elimination rate constants, and half-lives were 0.915 h(-1), 4.379 liters/kg, 0.00839 h(-1), and 5.5 days for PYR and 1.659 h(-1), 0.392 liters/kg, 0.00526 h(-1), and 6.6 days for SDX, respectively. Wide interindividual variability was observed. The estimated minimum and maximum concentrations of PYR in serum differed 8- and 25-fold among patients, respectively, and those of SDX differed 4- and 5-fold, respectively. Increases in the concentration of PYR were observed for eight children, and increases in the SDX concentration were observed for seven child...Continue Reading

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Citations

Jul 22, 2009·Antimicrobial Agents and Chemotherapy·Harin A KarunajeewaTimothy M E Davis
Jan 24, 2008·Antimicrobial Agents and Chemotherapy·Pascale MeneceurFrancis Derouin
Jul 27, 2007·Fetal Diagnosis and Therapy·Emmanouil GalanakisChristina Giannakopoulou
Nov 21, 2009·La Presse médicale·Patricia Garcia-MéricRenaud Piarroux
Nov 20, 2009·Journal of Clinical Microbiology·Emmanuelle ChapeyFrançois Peyron

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