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1.
Am J Vet Res ; 53(12): 2292-5, 1992 Dec.
Article in English | MEDLINE | ID: mdl-1476310

ABSTRACT

Single-dose pharmacokinetic variables of pyrimethamine were studied in horses. Pyrimethamine (1 mg/kg of body weight) was administered IV and orally to 6 adult horses, and plasma samples were obtained at frequent intervals thereafter. Plasma pyrimethamine concentration was assayed by gas chromatography, and concentration-time data were analyzed, using a pharmacokinetic computer program. The IV and oral administration data were best described by 3-compartment and 1-compartment models, respectively. The median volume of distribution at steady state after IV administration was 1,521 ml/kg and the median elimination half-time was 12.06 hours. Mean plasma concentration after oral administration fluctuated between a maximal concentration of 0.18 microgram/ml and 0.09 microgram/ml (24 hours after dosing). Bioavailability after oral administration was 56%.


Subject(s)
Horses/metabolism , Pyrimethamine/pharmacokinetics , Administration, Oral , Animals , Chromatography, Gas/veterinary , Female , Injections, Intravenous/veterinary , Male , Models, Biological , Pyrimethamine/blood
2.
Am J Vet Res ; 53(12): 2296-9, 1992 Dec.
Article in English | MEDLINE | ID: mdl-1476311

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.


Subject(s)
Horses/blood , Pyrimethamine/pharmacokinetics , Administration, Oral , Animals , Blood Cell Count/drug effects , Blood Cell Count/veterinary , Female , Horses/metabolism , Male , Models, Biological , Pyrimethamine/administration & dosage , Pyrimethamine/cerebrospinal fluid , Pyrimethamine/pharmacology
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