The study objective was to determine plasma concentration of
pyrimethamine in 24 infants aged 1-5 months, treated for
congenital toxoplasmosis.
Pyrimethamine was used in a single daily dose at an amount of 0.35-0.98 mg/kg daily, with
sulfadiazine (50-100 mg/kg/day) in divided doses 2-3 times a day, and
folinic acid given twice a week (7.5 mg). This regimen was continued for 2-6 months, then
Fansidar was administered.
Pyrimethamine concentration in plasma was measured using high-performance liquid chromatography method (HPLC). A total of 70 tests were performed. Concentration of
pyrimethamine ranged from 0.01 to 1.2 microg/ml. In 14 children (58 tests) the concentration of
pyrimethamine achieved therapeutic value. In 7 patients (8 tests) the concentration was below therapeutic level, and in 3 patients (4 tests) above therapeutic level. In 11/24 (46%) children transient moderate
neutropenia was observed. Modification of
therapy was necessary in 12 patients. Monitoring of
pyrimethamine concentration in plasma improves safety and effectiveness of the
therapy and is useful in obtaining correct individual dose of the
drug.
Neutropenia is the most common side-effect of
pyrimethamine observed even when using the recommended dose.