Summary
Pharmacokinetics, csf penetration, and hematologic effects of oral administration of pyrimethamine were studied after multiple dosing. Pyrimethamine (1 mg/kg of body weight) was administered orally once a day for 10 days to 5 adult horses, and blood samples were collected frequently after the first, fifth, and tenth doses. The csf samples were obtained by cisternal puncture 4 to 6 hours after administration of the first, third, seventh, and tenth doses. Pyrimethamine concentration in plasma and csf was quantified by gas chromatography, and plasma concentration-time data were analyzed, using a pharmacokinetic computer program. Repeated daily dosing resulted in accumulation of pyrimethamine in plasma, with steady state being achieved within 5 days, when the mean peak plasma concentration was more than twice that measured after the first dose. Pyrimethamine concentration in csf was 25 to 50% of corresponding plasma concentration and did not appear to accumulate with successive administration of doses. Blood samples collected during and after the dosing regimen were submitted for hematologic analysis; neutrophil numbers decreased slightly, but remained within normal range for adult horses.
