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Summary

Staggers was diagnosed in sheep and cattle from the northern California coast. The diagnosis was made on the basis of history of ingestion of perennial ryegrass (Lolium perenne) stubble, clinical signs of transient ataxia, which was aggravated by stimulation, and nearly complete recovery after removal of ryegrass as the primary forage. Morbidity was high, but death did not occur in any affected animals. The toxic endophyte, Acremonium lolii, was in most lower leaf sheaths from the ryegrass. Injection of extracts of the ryegrass from affected farms into mice induced signs of toxicosis. Additionally, ryegrass from all 3 farms contained the tremorgenic mycotoxin, lolitrem-B.

Free access
in Journal of the American Veterinary Medical Association

Abstract

Objective—To determine the pharmacokinetics of ceftiofur sodium after IM and SC administration in green iguanas.

Animals—6 male and 4 female adult green iguanas.

Procedure—In a crossover design, 5 iguanas received a single dose of ceftiofur sodium (5 mg/kg) IM, and 5 iguanas received the same dose SC. Blood samples were taken at 0, 20, and 40 minutes and 1, 2, 4, 8, 24, 48, and 72 hours after administration. After a 10-week washout period, each iguana was given the same dose via the reciprocal administration route, and blood was collected in the same fashion. Ceftiofur free-acid equivalents were measured via high-performance liquid chromatography.

Results—The first phase intercepts were significantly different between the 2 administration routes. Mean maximum plasma concentration was significantly higher with the IM (28.6 ± 8.0 µg/mL) than the SC (18.6 ± 8.3 µg/mL) administration route. There were no significant differences between terminal halflives (harmonic mean via IM route, 15.7 ± 4.7 hours; harmonic mean via SC route, 19.7 ± 6.7 hours) and mean areas under the curve measured to the last time point (IM route, 11,722 ± 7,907 µg·h/mL; SC route, 12,143 ± 9,633 µg·h/mL). Ceftiofur free-acid equivalent concentrations were maintained ≥ 2 µg/mL for > 24 hours via both routes.

Conclusions and Clinical Relevance—A suggested dosing schedule for ceftiofur sodium in green iguanas for microbes susceptible at > 2 µg/mL would be 5 mg/kg, IM or SC, every 24 hours. (Am J Vet Res 2003;64:1278–1282)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To describe pharmacokinetics of multidose oral administration of tacrolimus in healthy cats and evaluate the efficacy of tacrolimus in the prevention of allograft rejection in cats with renal transplants.

Animals—6 healthy research cats.

Procedure—Cats received tacrolimus (0.375 mg/kg, PO, q 12 h) for 14 days. Blood tacrolimus concentrations were measured by a high performance liquid chromatography-mass spectrometry assay. Each cat received an immunogenically mismatched renal allograft and native kidney nephrectomy. Tacrolimus dosage was modified to maintain a target blood concentration of 5 to 10 ng/mL. Cats were euthanatized if plasma creatinine concentration exceeded 7 mg/dL, body weight loss exceeded 20%, or on day 50 after surgery. Kaplan-Meier survival curves were plotted for 6 cats treated with tacrolimus and for 8 cats with renal transplants that did not receive immunosuppressive treatment.

Results—Mean (± SD) values of elimination half-life, time to maximum concentration, maximum blood concentration, and area under the concentration versus time curve from the last dose of tacrolimus to 12 hours later were 20.5 ± 9.8 hours, 0.77 ± 0.37 hours, 27.5 ± 31.8 ng/mL, and 161 ± 168 hours × ng/mL, respectively. Tacrolimus treated cats survived longer (median, 44 days; range, 24 to 52 days) than untreated cats (median, 23 days; range, 8 to 34 days). On histologic evaluation, 3 cats had evidence of acute-active rejection, 1 cat had necrotizing vasculitis, and 2 cats euthanatized at study termination had normal appearing allografts.

Conclusions and Clinical Relevance—Tacrolimus may be an effective immunosuppressive agent for renal transplantation in cats. (Am J Vet Res 2003;64:926–934)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the pharmacokinetics of butorphanol tartrate after IV and IM single-dose administration in red-tailed hawks (RTHs) and great horned owls (GHOs).

Animals—6 adult RTHs and 6 adult GHOs.

Procedures—Each bird received an injection of butorphanol (0.5 mg/kg) into either the right jugular vein (IVj) or the pectoral muscles in a crossover study (1-week interval between treatments). The GHOs also later received butorphanol (0.5 mg/kg) via injection into a medial metatarsal vein (IVm). During each 24-hour postinjection period, blood samples were collected from each bird; plasma butorphanol concentrations were determined via liquid chromatography-mass spectrometry.

Results—2- and 1-compartment models best fit the IV and IM pharmacokinetic data, respectively, in both species. Terminal half-lives of butorphanol were 0.94 ± 0.30 hours (IVj) and 0.94 ± 0.26 hours (IM) for RTHs and 1.79 ± 1.36 hours (IVj), 1.84 ± 1.56 hours (IM), and 1.19 ± 0.34 hours (IVm) for GHOs. In GHOs, area under the curve (0 to infinity) for butorphanol after IVj or IM administration exceeded values in RTHs; GHO values after IM and IVm administration were less than those after IVj administration. Plasma butorphanol clearance was significantly more rapid in the RTHs. Bioavailability of butorphanol administered IM was 97.6 ± 33.2% (RTHs) and 88.8 ± 4.8% (GHOs).

Conclusions and Clinical Relevance—In RTHs and GHOs, butorphanol was rapidly absorbed and distributed via all routes of administration; the drug's rapid terminal half-life indicated that published dosing intervals for birds may be inadequate in RTHs and GHOs.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To investigate the feasibility of using multivariate cluster analysis to meta-analyze pharmacokinetic data obtained from studies of pharmacokinetics of ampicillin trihydrate in cattle and identify factors that could account for variability in pharmacokinetic parameters among studies.

Sample Population—Data from original studies of the pharmacokinetics of ampicillin trihydrate in cattle in the database of the Food Animal Residue Avoidance Databank.

Procedure—Mean plasma or serum ampicillin concentration versus time data and potential factors that may have affected the pharmacokinetics of ampicillin trihydrate were obtained from each study. Noncompartmental pharmacokinetic analyses were performed, and values of pharmacokinetic parameters were clustered by use of multivariate cluster analysis. Practical importance of the clusters was evaluated by comparing the frequency of factors that may have affected the pharmacokinetics of ampicillin trihydrate among clusters.

Results—A single cluster with lower mean values for clearance and volume of distribution of ampicillin trihydrate administered PO, compared with other clusters, was identified. This cluster included studies that used preruminant calves in which feeding was withheld overnight and calves to which probenecid had been administered concurrently.

Conclusions and Clinical Relevance—Meta-analysis was successful in detecting a potential subpopulation of cattle for which factors that explained differences in pharmacokinetic parameters could be identified. Accurate estimates of pharmacokinetic parameters are important for the calculation of dosages and extended withdrawal intervals after extralabel drug administration. (Am J Vet Res 2005;66:108–112)

Full access
in American Journal of Veterinary Research
in Journal of the American Veterinary Medical Association
in Journal of the American Veterinary Medical Association
in Journal of the American Veterinary Medical Association