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Davis, J. L., Marshall, J. F., Papich, M. G., Blikslager, A. T., Campbell, N. B. The pharmacokinetics and in vitro cyclooxygenase selectivity of deracoxib in horses. J. vet. Pharmacol. Therap. 34 , 12–16. The purpose of this study was to determine the pharmacokinetics of deracoxib following oral administration to horses. In addition, in vitro equine whole blood cyclooxygenase (COX) selectivity assays were performed. Six healthy adult horses were administered deracoxib (2 mg/kg) orally. Plasma samples were collected prior to drug administration (time 0), and 10, 20, 40 min and 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 h after administration for analysis with high pressure liquid chromatography using ultraviolet detection. Following PO administration, deracoxib had a long elimination half‐life (t1/2k10) of 12.49 ± 1.84 h. The average maximum plasma concentration (Cmax) was 0.54 μg/mL, and was reached at 6.33 ± 3.44 h. Bioavailability was not determined because of the lack of an IV formulation. Results of in vitro COX selectivity assays showed that deracoxib was selective for COX‐2 with a COX‐1/COX‐2 ratio of 25.67 and 22.06 for the IC50 and IC80, respectively. Dosing simulations showed that concentrations above the IC80 for COX‐2 would be maintained following 2 mg/kg PO q12h, and above the IC50 following 2 mg/kg PO q24h. This study showed that deracoxib is absorbed in the horse after oral administration, and may offer a useful alternative for anti‐inflammatory treatment of various conditions in the horse.  相似文献   
63.
Musulin, S. E., Mariani, C. L., Papich, M. G. Diazepam pharmacokinetics after nasal drop and atomized nasal administration in dogs. J. vet. Pharmacol. Therap. 34 , 17–24. The standard of care for emergency therapy of seizures in veterinary patients is intravenous (i.v.) administration of benzodiazepines, although rectal administration of diazepam is often recommended for out‐of‐hospital situations, or when i.v. access has not been established. However, both of these routes have potential limitations. This study investigated the pharmacokinetics of diazepam following i.v., intranasal (i.n.) drop and atomized nasal administration in dogs. Six dogs were administered diazepam (0.5 mg/kg) via all three routes following a randomized block design. Plasma samples were collected and concentrations of diazepam and its active metabolites, oxazepam and desmethyldiazepam were quantified with high‐performance liquid chromatography (HPLC). Mean diazepam concentrations >300 ng/mL were reached within 5 min in both i.n. groups. Diazepam was converted into its metabolites within 5 and 10 min, respectively, after i.v. and i.n. administration. The half lives of the metabolites were longer than that of the parent drug after both routes of administration. The bioavailability of diazepam after i.n. drop and atomized nasal administration was 42% and 41%, respectively. These values exceed previously published bioavailability data for rectal administration of diazepam in dogs. This study confirms that i.n. administration of diazepam yields rapid anticonvulsant concentrations of diazepam in the dog before a hepatic first‐pass effect.  相似文献   
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Pharmacokinetics of procainamide hydrochloride were studied in 2 groups of dogs. In a group of 6 dogs, procainamide was administered IV at a small dose of 8 mg/kg (group 1), and blood samples were obtained for 3.5 hours. In another group of 6 dogs, procainamide was administered IV and orally at an average dose of 25.5 mg/kg (group 2) in a crossover manner. Blood samples were obtained for 48 hours. In 2 dogs (previously used in part II), N-acetylprocainamide (NAPA) was administered IV at a dose of 10 mg/kg. Plasma samples were assayed for procainamide by fluorescence polarization immunoassay, and NAPA samples were assayed by high-performance liquid chromatography. In group 1, the elimination of procainamide was described by a 1-compartment, open pharmacokinetic model. The elimination half-life was 2.43 hours, the apparent volume of distribution was 1.44 L/kg, and the systemic clearance was 0.412 L/kg/hr. In group 2, 2 of the 6 dogs were described by a 1-compartment model, and 4 of the 6 dogs were described with a 2-compartment pharmacokinetic model. The elimination half-life for the IV dosage was 2.85 hours, the apparent volume of distribution was 2.13 L/kg, and the systemic clearance was 0.519 L/kg/hr. For the orally administered dose, the bioavailability was 85%, and the absorption half-life was 0.5 hours. There was no evidence of acetylation of procainamide to NAPA or deacetylation of NAPA to procainamide. The estimated elimination half-life of NAPA was 4.7 hours.  相似文献   
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This study documents the pharmacokinetics of oral tramadol in Muscovy ducks. Six ducks received a single 30 mg/kg dose of tramadol, orally by stomach tube, with blood collection prior to and up to 24 hr after tramadol administration. Plasma tramadol, and metabolites O‐desmethyltramadol (M1), and N,O‐didesmethyltramadol (M5) concentrations were determined by high‐pressure liquid chromatography (HPLC) with fluorescence (FL) detection. Pharmacokinetic parameters were calculated using a one‐compartment model with first‐order input. No adverse effects were noted after oral administration. All ducks achieved plasma concentrations of tramadol above 0.10 μg/ml and maintained those concentrations for at least 12 hr. Elimination half‐life was 3.95 hr for tramadol in ducks, which is similar to other avian species. All ducks in this study produced the M1 metabolite and maintained plasma concentrations above 0.1 μg/ml for at least 24 hr.  相似文献   
68.
This study's objectives were to determine intestinal antimicrobial concentrations in calves administered enrofloxacin or ceftiofur sodium subcutaneously, and their impact on representative enteric bacteria. Ultrafiltration devices were implanted in the ileum and colon of 12 steers, which received either enrofloxacin or ceftiofur sodium. Samples were collected over 48 h after drug administration for pharmacokinetic/pharmacodynamic analysis. Enterococcus faecalis or Salmonella enterica (5 × 105 CFU/mL of each) were exposed in vitro to peak and tail (48 h postadministration) concentrations of both drugs at each location for 24 h to determine inhibition of growth and change in MIC. Enrofloxacin had tissue penetration factors of 1.6 and 2.5 in the ileum and colon, while ciprofloxacin, an active metabolite of enrofloxacin, was less able to cross into the intestine (tissue penetration factors of 0.7 and 1.7). Ceftiofur was rapidly eliminated leading to tissue penetration factors of 0.39 and 0.25. All concentrations of enrofloxacin were bactericidal for S. enterica and significantly reduced E. faecalis. Peak ceftiofur concentration was bactericidal for S. enterica, and tail concentrations significantly reduced growth. E. faecalis experienced growth at all ceftiofur concentrations. The MICs for both organisms exposed to peak and tail concentrations of antimicrobials were unchanged at the end of the study. Enrofloxacin and ceftiofur achieved intestinal concentrations capable of reducing intestinal bacteria, yet the short exposure of ceftiofur in the intestine may select for resistant organisms.  相似文献   
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Ceftazidime, a third‐generation cephalosporin, is important for treating opportunistic bacterial infections in turtles. Antibacterial dosage regimens are not well established for wild turtles and are often extrapolated from other reptiles or mammals. This investigation used a population pharmacokinetic approach to study ceftazidime in wild turtles presented for rehabilitation. Ceftazidime was administered to 24 wild turtles presented to the Turtle Rescue Team at North Carolina State University. A sparse blood sampling protocol was used to collect samples from 0 to 120 hr with three samples per individual after injection. Plasma samples were analyzed by high‐pressure liquid chromatography (HPLC). A nonlinear mixed‐effects model (NLME) was fitted to the data to determine typical values for population parameters. We identified a long half‐life (T½) of approximately 35 hr and volume of distribution (VSS) of 0.26 L/kg. We concluded that this long T½ will allow for a dose of 20 mg/kg injected IM to maintain concentrations above the MIC of most wild‐type bacteria for 5 days. Because of long intervals between injections, stability of stored formulations was measured and showed that 90% strength was maintained for 120 hr when stored in the refrigerator and for 25 days when stored in the freezer.  相似文献   
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