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  • Author or Editor: George E. Burrows x
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Summary

A subcutaneous soft tissue infection model in calves was used to study the in vivo response of Pasteurella haemolytica to erythromycin and dexamethasone. Two tissue chambers were implanted sc in each of 12 calves. At 45 days after implantation, all tissue chambers were inoculated with an erythromycin-sensitive strain of P haemolytica. Starting 24 hours after inoculation, calves were allotted to 4 groups of equal size and a 2 × 2-factorial arrangement of treatments was applied: 3 calves were given erythromycin (30 mg/kg of body weight, im, for 5 days), 3 calves were given dexamethasone(0.05 mg/kg, im, for 2 days), 3 calves were given erythromycin and dexamethasone, and the remaining calves served as nontreated controls. Chamber fluids were tested daily, and the response to treatment was measured. Neither erythromycin nor dexamethasone affected viability or growth of bacteria within tissue chambers. Dexamethasone had no effect on the influx of neutrophils into infected chambers. Despite repeated administration of a high dose of erythromycin and attainment of adequate concentration in serum, erythromycin concentration in chamber fluids did not exceed the minimal inhibitory concentration established in vitro. These results indicate that the clinical efficacy of erythromycin against P haemolytica sequestered in consolidated pneumonic lesions may not be well correlated with predictions based on serum pharmacokinetic and in vitro susceptibility data.

Free access
in American Journal of Veterinary Research

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.

Free access
in American Journal of Veterinary Research

Summary

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 µg/ml and 0.09 µg/ml (24 hours after dosing). Bioavailability after oral administration was 56%.

Free access
in American Journal of Veterinary Research