title: Pharmacokinetics, penetration into cerebrospinal fluid, and hematologic effects after multiple oral administrations of pyrimethamine to horses.
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.
authors: Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater 74078.
authors: C R
authors: CR
authors: Clarke
authors: C G
authors: CG
authors: MacAllister
authors: G E
authors: GE
authors: Burrows
authors: P
authors: P
authors: Ewing
authors: D K
authors: DK
authors: Spillers
authors: S L
authors: SL
authors: Burrows
mesh_terms: 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
chemical_list: D011739:Pyrimethamine