Pharmacokinetics, penetration into cerebrospinal fluid, and hematologic effects after multiple oral administrations of pyrimethamine to horses. |
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Authors: | C R Clarke C G MacAllister G E Burrows P Ewing D K Spillers S L Burrows |
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Affiliation: | Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater 74078. |
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Abstract: | 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. |
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