The in vitro erythromycin-binding properties of bovine alpha-1-acid glycoprotein (AAG) and albumin were studied by using equilibrium dialysis. In addition, the proportions of free erythromycin in bovine serum and tissue chamber fluid before and 4 days after inoculation of subcutaneous tissue chambers with Pasteurella haemolytica were measured. At a concentration of 5 micrograms/ml, erythromycin was moderately bound to AAG (39% +/- 4% free) and was only slightly bound to albumin (86% +/- 2% free). Scatchard analysis of the data describing binding to pure bovine AAG indicated that erythromycin was bound to a single high-affinity (6.45 x 10(4) M-1) site on the protein. At lower total concentrations of erythromycin, the free concentrations of the antibiotic were lower in serum samples collected after infection (49% +/- 3% at 5 micrograms of erythromycin per ml) than in those collected before inoculation (55% +/- 3% at 5 micrograms of erythromycin per ml). Inoculation had no effect on binding to macromolecules in chamber fluids. Inoculated tissue chambers served as a convenient model for studying the effect of infection on drug-macromolecule interactions in interstitial fluid.
To investigate intraocular penetration of orally administered doxycycline in the normal equine eye and to compare intraocular and serum doxycycline concentrations. Procedures Six mares were administered doxycycline at 10 mg/kg every 12 h by nasogastric tube for 5 days. Blood, aqueous, and vitreous samples were collected on days 1 and 5. All samples were assayed for doxycycline concentrations. Aqueous and vitreous samples were also assayed for protein quantitation.Doxycycline was rapidly absorbed after the first dose (T(max) value of 1.42 +/- 1.28 h); and elimination of doxycycline occurred slowly (median t(1/2) = 10.88 h). Doxycycline could not be detected in the aqueous on days 1 and 5, nor could it be detected in the vitreous on day 1. On day 5, the mean vitreous doxycycline concentration was 0.17 +/- 0.04 microg/mL at 2 h after drug administration.Repeated oral administration of doxycycline in the horse resulted in steady state serum concentrations of < 1 microg/mL; however, it did not result in appreciable concentrations of drug in the aqueous and vitreous in normal eyes.
SUMMARY A study was designed to develop and define a sc tissue chamber as a suitable device for establishing a soft-tissue infection model in cattle and to use this model to study the interaction between Pasteurella haemolytica , sulfadiazine/trimethoprim, and bovine viral diarrhea virus ( bvdv ). Thermoplastic tissue chambers were implanted in the paralumbar fossae of 20 calves. At 35 days after implantation, calves were allotted to 4 groups of equal size and the calves in 2 groups were inoculated intratracheally with a New York-1 strain of bvdv . At 45 days after implantation, all chambers were inoculated with a 6-hour culture of P haemolytica serotype 1. Starting 36 hours after bacterial inoculation, sulfadiazine/trimethoprim was administered iv once a day to half of the virus-inoculated calves and to half of those calves that had not been exposed to virus. Inoculation of P haemolytica into tissue chambers resulted in the establishment of a localized soft-tissue infection, characteristic of pneumonic pasteurellosis. Despite the maintenance of chamber antimicrobial concentrations that exceeded minimal bactericidal concentrations established in vitro, the infections were not sterilized. This lack of efficacy was associated with decreased pH and increased protein concentrations in chamber fluids after inoculation. Infection with bvdv , which is thought to depress host defenses, had no effect on the response of P haemolytica to sulfadiazine/trimethoprim administration. Observation of responsive antibody titers, bacterial phagocytosis, and high leukocyte viability within P haemolytica -infected chambers documented functional host defenses within tissue chambers.
Abstract Objective —To use force plate analysis to evaluate the analgesic efficacies of flunixin meglumine and phenylbutazone administered IV at typical clinical doses in horses with navicular syndrome. Animals —12 horses with navicular syndrome that were otherwise clinically normal. Procedure —Horses received flunixin (1.1 mg/kg), phenylbutazone (4.4 mg/kg), or physiologic saline (0.9% NaCl; 1 mL/45 kg) solution administered IV once daily for 4 days with a 14-day washout period between treatments (3 treatments/horse). Before beginning treatment (baseline) and 6, 12, 24, and 30 hours after the fourth dose of each treatment, horses were evaluated by use of the American Association of Equine Practitioners lameness scoring system (half scores permitted) and peak vertical force of the forelimbs was measured via a force plate. Results —At 6, 12, and 24 hours after the fourth treatment, subjective lameness evaluations and force plate data indicated significant improvement in lameness from baseline values in horses treated with flunixin or phenylbutazone, compared with control horses; at those time points, the assessed variables in flunixin- or phenylbutazone-treated horses were not significantly different. Conclusions and Clinical Relevance —In horses with navicular syndrome treated once daily for 4 days, typical clinical doses of flunixin and phenylbutazone resulted in similar significant improvement in lameness at 6, 12, and 24 hours after the final dose, compared with findings in horses treated with saline solution. The effect of flunixin or phenylbutazone was maintained for at least 24 hours. Flunixin meglumine and phenylbutazone appear to have similar analgesic effects in horses with navicular syndrome. ( Am J Vet Res 2005;66:284–288)
A soft-tissue infection model was created in eight horses by infecting subcutaneous tissue chambers with Streptococcus zooepidemicus organisms. Responses of the horses to the infections were determined by monitoring changes in the complete blood count and body temperature and by following changes in the cytology and protein content of the tissue chambers. Systemic reactions to the infections included a mild neutrophilia, mild pyrexia and mild anemia. There was a marked influx of neutrophils and protein into the chambers after they were seeded with bacteria and chamber neutrophil viability decreased markedly at the height of the infection. Subsequent to establishing tissue chamber infections four of the horses were treated with intravenous cephapirin t.d. at a dosage of 20 mg/kg for 5 days. Quantitative culturing of tissue chamber fluid was performed to analyze the efficacy of cephapirin therapy. Cephapirin therapy was accompanied by decreases in the systemic neutrophilia, pyrexia, anemia, and chamber bacterial counts. However, cephapirin did not eliminate the infection in any of the chambers. Chamber neutrophil viability was markedly increased during the cephapirin therapy period.
SUMMARY The purpose of this study was to determine the pharmacokinetic values for gentamicin in neonatal calves and to compare these values with those in adult cattle (cows). Gentamicin (4 mg/kg of body weight) was administered iv to 7 Holstein bull calves on days 1 (between 12 and 24 hours of age), 5, 10, and 15 after birth, and was administered once iv to 7 Holstein cows. Serum was collected from each animal before administration and at 22 different time intervals from 2 to 400 minutes after injection. Sera were analyzed for gentamicin concentrations. Decay of serum gentamicin concentrations was best described by a 2-compartment pharmacokinetic model. Elimination half-life (t ½ (β) ) of gentamicin decreased from day 1 (149 minutes) to day 5 (119 minutes), but did not change between days 5 and 15 (111 minutes). Compared with the t ½ (β) in 1- and 15-day-old calves, the t ½ (β) in cows was shorter (76 minutes). In the calves, apparent volume of distribution (based on total area under the disposition curve) did not change between 1 (393 ml/kg) and 5 (413 ml/kg) days of age, decreased on day 10 (341 ml/kg) and cows day 15 (334 ml/kg), and was markedly smaller than that in cows (140 ml/kg). Total body clearance of gentamicin in cows (1.29 ml/min·kg) was lower than that seen in calves on day 1 (1.92 ml/min·kg) and on day 15 (2.10 ml/min·kg). The decrease in apparent volume of distribution of gentamicin was mirrored by a large decrease in the extracellular fluid volume, as measured by inulin space. Age-related changes in total body water were not found, as measured by antipyrine space. The percentage protein binding of gentamicin was < 30%.
Naloxone is an opioid antagonist used frequently in studies of appetite regulation in lean and obese animals and humans. Body condition may affect plasma and tissue distribution of injected naloxone and thus confound interpretation of responses to naloxone in lean compared with obese subjects. The objective of this experiment was to determine the effect of dietary obesity per se on the pharmacokinetic behavior of iv-injected naloxone (3 mg/kg) in lean (46 kg body weight) and dietary obese (77 kg body weight) sheep that were maintained at equilibrium weight. To this end, an HPLC procedure combined with electrochemical detection was developed for measuring naloxone in sheep plasma. Naloxone disappearance from plasma followed an apparent first-order process, the kinetics of which were described best using a two-compartment open model. Components of the biexponential equations describing the plasma concentration (C) – time (t) curves for naloxone disappearance in lean (C t = 1814e −0.190t + 413e −0.017t ) and obese (C t = 2282e −0.282t + 573e −0.018t ) sheep were similar (p > 0.05). Mean (±SE) elimination half-lifes for naloxone in lean (42.7 ± 4.6 min) and obese (44.3 ± 10.2 min) sheep were similar (p > 0.05). Volume of distribution of naloxone (V d ) was extensive but also similar (p > 0.05) in lean (5.6 ± 0.9 L/kg) and obese (4.1 ± 0.6 L/kg) sheep. Naloxone was distributed extensively throughout the body fluids and trapped or stored in significant amount in extravascular tissues because the naloxone V d greatly exceeded 100% of body weight in both lean (557 ± 86 mL/100 g) and obese (413 ± 58 mL/100 g) sheep. Whole-body clearance (Cl B ) of naloxone indexed to body weight (90 ± 7 vs. 69 ± 6 mL∙kg −1 ∙min −1 ) and absolute rates for body clearance (4.1 ± 0.3 vs. 5.3 ± 0.6 L/min) of naloxone tended to be greater (p < 0.1) in lean than obese sheep. We conclude that dietary obesity did not alter significantly the pharmacokinetic behavior of iv-injected naloxone in sheep.Key words: naloxone, obesity, sheep, kinetics, HPLC.
