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  • Author or Editor: Steven Budsberg x
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SUMMARY

Cortical bone concentrations of enrofloxacin were determined over time in dogs after sc administration of the drug. Nineteen healthy adult dogs were anesthetized and were given 2.5 or 5.0 mg of enrofloxacin/kg of body weight, sc. Serial serum and bone samples were obtained for determination of enrofloxacin concentrations at intervals until 8 hours after drug administration. Cortical bone samples were procured by surgical disarticulation of successive second phalanges. Additional cortical bone samples were taken from long bones in 4 dogs. Mean ± sd peak serum enrofloxacin concentration was 0.54 ± 0.10 μg/ml for the 2.5-mg/kg dosage and 0.97 ± 0.34 μg/ml for the 5.0-mg/kg dosage. Serum concentration was significantly higher than bone concentration for each dosage. Mean peak bone concentrations reached 29% of peak serum values: 0.15 ± 0.09 μg/g and 0.29 ± 0.09 μg/g for 2.5-mg/kg and 5.0-mg/kg dosages, respectively. Serum concentration for the 5.0-mg/kg dosage was significantly greater than that for the 2.5-mg/kg dosage for all times, whereas bone concentrations for the 5.0-mg/kg dosage were significantly higher at all times after 180 minutes. For the duration of the study, cortical bone concentrations of enrofloxacin at either dosage exceeded the minimum inhibitory concentration (mic) for the Enterobacteriaceae, but reliably exceeded the mic for Staphylococcus sp only at the 5.0-mg/kg dosage. At no time did cortical bone concentrations of enrofloxacin exceed the mic for Pseudomonas aeruginosa at either dosage.

To validate extrapolation of data from the second phalanx to long bones and from anesthetized to awake dogs, 16 healthy dogs being euthanatized in unrelated studies were given 2.5 or 5.0 mg of enrofloxacin/kg, sc. These dogs were not anesthetized but were euthanatized at 60, 120, or 240 minutes after drug administration, and multiple cortical bone samples were taken. Antibiotic concentrations in the second phalanx were not significantly different from those in long bones. Comparison of enrofloxacin concentrations in cortical bone of awake and anesthetized dogs suggested no differences between groups. We concluded that general anesthesia and use of the antibiotic concentrations in the second phalanx as representative of those in long bones did not affect results of this study.

Free access
in American Journal of Veterinary Research

Abstract

Objective—To determine pharmacodynamic and pharmacokinetic properties of clopidogrel and the metabolite SR 26334 in dogs.

Animals—9 mixed-breed dogs.

Procedures—8 dogs received clopidogrel (mean ± SD 1.13 ± 0.17 mg/kg, PO, q 24 h) for 3 days; 5 of these dogs subsequently received a lower dose of clopidogrel (0.5 ± 0.18 mg/kg, PO, q 24 h) for 3 days. Later, 5 dogs received clopidogrel (1.09 ± 0.12 mg/kg, PO, q 24 h) for 5 days. Blood samples were collected for optical platelet aggregometry, citrated native and platelet mapping thrombelastography (TEG), and measurement of plasma drug concentrations. Impedance aggregometry was performed on samples from 3 dogs in each 3-day treatment group.

Results—ADP-induced platelet aggregation decreased (mean ± SD 93 ± 6% and 80 ± 22% of baseline values, respectively) after 72 hours in dogs in both 3-day treatment groups; duration of effect ranged from > 3 to > 7 days. Platelet mapping TEG and impedance aggregometry yielded similar results. Citrated native TEG was not different among groups. Clopidogrel was not detected in any samples; in dogs given 1.13 ± 0.17 mg/kg, maximum concentration of SR 26334 (mean ± SD, 0.206 ± 0.2 μg/mL) was detected 1 hour after administration.

Conclusions and Clinical Relevance—Clopidogrel inhibited ADP-induced platelet aggregation in healthy dogs and may be a viable antiplatelet agent for use in dogs.

Impact for Human Medicine—Pharmacodynamic effects of clopidogrel in dogs were similar to effects reported in humans; clopidogrel may be useful in studies involving dogs used to investigate human disease.

Full access
in American Journal of Veterinary Research

Summary

Ciprofloxacin, a fluoroquinolone antimicrobial agent, was administered orally to 4 healthy dogs at dosage of approximately 11 and 23 mg/kg of body weight, every 12 hours for 4 days, with a 4-week interval between dosing regimens. Serum and tissue cage fluid (tcf) concentrations of ciprofloxacin were measured after the first and seventh dose of each dosing regimen. The peak concentration was greatest in the serum after multiple doses of 23 mg/kg (mean ± sem; 5.68 ± 0.54 μg/ml) and least in the tcf after a single dose of 11 mg/kg (0.43 ± 0.54 μg/ml). The time to peak concentration was not influenced by multiple dosing or drug dose, but was longer for tcf (6.41 ± 0.52 hour) than for serum (1.53 ± 0.52 hour). Accumulation of ciprofloxacin was reflected by the area under the concentration curve from 0 to 12 hours after administration (AUC0→12). The AUC0→12 was greatest in the serum after multiple doses of 23 mg/kg (31.95 ± 1.90 μg·h/ml) and least in the tcf after a single dose of 11 mg/kg (3.87 ± 1.90 μg·h/ml). The elimination half-life was not influenced by multiple dosing or dose concentration, but was greater for tcf (14.59 ± 1.91 hours) than for serum (5.14 ± 1.91 hours). The percentage of tcf penetration (AUCTCF/AUCserum ) was greater after multiple doses (95.76 ± 6.79%) than after a single dose (55.55 ± 6.79%) and was not different between doses of 11 and 23 mg/kg. Both dosing regimens of ciprofloxacin resulted in continuous serum and tcf concentrations > 90% of the minimal inhibitory concentration for the aerobic and facultative anaerobic clinical isolates tested, including Pseudomonas aeruginosa.

Free access
in American Journal of Veterinary Research