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Pharmacokinetics of single-dose administration of moxalactam in umweaned calves
1989
Soback, S.
Twenty-nine healthy 17- to 29-day-old unweaned Isaeli-Friesian male calves were each given a single IV or IM injection of 10 or 20 mg of moxalactam disodium/kg of body weight. Serum concentrations were measured serially during a 12-hour period. Serum concentration vs time profiles were analyzed by use of linear least-squares regression analysis and the statistical moment theory. The elimination half-lives after IV administration were 143.7 +/- 30.2 minutes and 155.5 +/- 10.5 minutes (harmonic mean +/ SD) at dosages of 10 and 20 mg of moxalactam/kg of body weight, respectively. Corresponding mean residence time values were 153.1 +/- 26.8 minutes and 169.9 +/- 19.3 minutes (arithmetic mean +/- SD). Mean residence time values after IM administration were 200.4 +/- 17.5 minutes and 198.4 +/- 19.9 minutes at dosages of 10 and 20 mg/kg, respectively. The volumes of distribution at steady state were 0.285 +/- 0.073 L/kg and 0.313 +/- 0.020 L/kg and total body clearance values were 1.96 +/- 0.69 ml/min/kg and 1.86 +/- 0.18 ml/min/kg after administration of dosages of 10 and 20 mg/kg, respectively. Moxalactam was rapidly absorbed from the IM injection site and peak serum concentrations occurred at 1 hour. The estimated bioavailability ranged from 69.8 to 79.1%. The amount of serum protein binding was 53.4, 55.0, and 61.5% when a concentration of moxalactam was at 50, 10, and 2 micrograms/ml respectively. The minimal inhibitory concentrations of moxalactam ranged from 0.01 to 0.2 micrograms/ml against Salmonella and Escherichia coli strains and from 0.005 to 6.25 micrograms/ml against Pasteurella multocida strains.
Показать больше [+] Меньше [-]Pharmacokinetics of ceftazidime given alone and in combination with probenecid to unweaned calves
1989
Soback, S. | Ziv, G.
Ceftazidime pharmacokinetic values were studied in unweaned calves given the antibiotic alone or in combination with probenecid. Ceftazidime was administered IV to 9 calves at a dosage of 10 mg/kg of body weight and IM (10 mg/kg) to 8 calves, to 7 calves (10 mg/kg plus probenecid [40 mg/kg]), and to 9 calves (10 mg/kg plus probenecid [80 mg/kg]). Serum concentration-vs-time data were analyzed, using noncompartmental methods based on statistical moment theory. The data for IV ceftazidime administration also were fitted by use of a linear, open 2-compartment model. The mean (+/- SD) terminal half-life was 138.7 +/- 23.6 minutes and 126.3 +/- 10.5 minutes after IV and IM administrations, respectively. The mean residence time was 167.3 +/- 21.1 minutes and 201.4 +/- 16.8 minutes after IV and IM administrations, respectively. Coadministration of probenecid did not affect the terminal half-life or mean residence time values. The total body clearance was 1.75 +/- 0.26 ml/min/kg, and the volume of distribution at steady state was 0.294 +/- 0.064 L/kg. The estimated mean absorption time was 34.1 minutes. There were no significant differences between the mean residence time calculated by statistical moment theory or by compartmental analysis, indicating central compartment output of ceftazidime. The 90% minimal inhibitory concentration values of ceftazidime determined for Escherichia coli, Salmonella spp, Pasteurella multocida, and P haemolytica isolates ranged from less than 0.01 to 0.1 microgram/microliter.
Показать больше [+] Меньше [-]Detection of Salmonella dublin mammary gland infection in carrier cows, using an enzyme-linked immunosorbent assay for antibody in milk or serum
1989
Smith, B.P. | Oliver, D.G. | Singh, P. | Dilling, G. | Marvin, P.A. | Ram, B.P. | Jang, L.S. | Sharkov, N. | Orsborn, J.S. | Jackett, K.
An ELISA has been developed for measurement of milk and serum IgG concentrations directed against Salmonella dublin. Four groups of cows were studied: group A-7 experimentally challenge-exposed cows (infected, recovered group); group B-6 normal uninfected randomly selected control cows; group C-7 naturally occurring S dublin carrier cows; and group D-6 normal uninfected S dublin negative cows from the same herd as group C. Group-A cows were inoculated orally, or inoculated orally and then IV, but none became a S dublin carrier. As expected, all 7 group-A cows responded with a marked increase in ELISA titer after oral exposure to virulent S dublin, starting with a mean serum titer of 17.7% and reaching a peak mean serum titer of 79.3% approximately 76 days after initial exposure. As determined by necropsy and organ culturing of the remaining cows, none of the group-A cows became carriers. The mean serum ELISA titer for group-B uninfected control cows was 14.1% (SD +/- 12.8%). The mean milk ELISA titer was -1.0% (SD +/- 5.5%). Colostrum and then milk gave false-positive results for up to 2 weeks after onset of lactation. Group-B cows were culture negative for S dublin in feces and milk during lactation, and when tissues were cultured after euthanasia. Milk and serum samples for ELISA, and milk and fecal samples for culturing were taken from all group-A and -B cows twice a week for 6 months. Statistical correlation (P less than 0.05) was found between serum and milk ELISA titers. A highly significant (P less than 0.001) difference in serum ELISA titers was demonstrated between control (group B) and infected cows (group A). Milk and feces from group-C carrier cows were cultured for S dublin 5 days a week for 11 to 13 months. Six of the 7 cows calved during this period. Fecal shedding was sporadic in 7 cows. Milk shedding was frequent in certain quarters of 4 of the cows and was sporadic or absent in other quarters of these cows and it was sporadic in 2 cows, and 1 cow had culture-positive milk only twice. The overall milk-shedding rate was 46% (792 positives/1,733 samples), whereas the overall fecal-shedding rate was 4% (65 positives/1,733 samples). Shedding in the 4 weeks after parturition was 28% in milk and 5% in feces. Six group-C cows had strongly positive ELISA titers in serum and milk, whereas 1 cow (the cow that had only 2 positive milk cultures) had relatively low ELISA titers. Group-C cows had a mean serum titer of 85.2% (SD +/- 19%) and mean milk titer of 70.6% (SD +/- 35.5%). These results indicate that IgG ELISA may be useful in detection of S dublin milk shedding (mammary gland infection) carrier cows. Milk shedding in the 4 persistent shedders ranged from 10(1) to 10(5) organisms/ml, and was associated with evidence of chronic active mastitis. Group-D cows, culture-negative herd mates of group-C carrier cows, were monitored in a manner identical to that used for group-C cows. All cows remained culture-negative for S dublin in feces and milk and results of organ culturing were negative for S dublin after euthanasia. The ELISA titers remained negative, with a mean group-D titer of 8 +/- 7.7% on serum, and 0.6 +/- 5.5% on milk. A highly significant difference in serum (P less than 0.0001) and milk (P less than 0.0001) ELISA titers was demonstrated between group-C carrier cows and group-D uninfected herd mates.
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