Pharmacokinetics, penetration into cerebrospinal fluid, and hematologic effects after multiple oral administrations of pyrimethamine to horses.
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.
Clarke
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CR
Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater 74078.
MacAllister
C G
CG
Burrows
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GE
Ewing
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P
Spillers
D K
DK
Burrows
S L
SL
D000284:Administration, Oral; D000818:Animals; D001772:Blood Cell Count / Q000187:drug effects / Q000662:veterinary; D005260:Female; D006736:Horses / Q000097:blood* / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D011739:Pyrimethamine / Q000008:administration & dosage / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics* / Q000494:pharmacology
D011739:Pyrimethamine