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  • Author or Editor: Mark G. Stevens x
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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.

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in American Journal of Veterinary Research


The effects of the skeletal muscle-relaxing drug dantrolene sodium alone, and in combination with the α1-adrenergic antagonist prazosin, on the urethral pressure profile were investigated in male cats with obstructive lower urinary tract disease. Decreases in mean segmental intraurethral pressure induced by dantrolene (n = 3) or dantrolene in combination with prazosin (n = 3) were evaluated statistically, using a paired design. Statistical analysis was applied to absolute (mm of Hg) pressure values. Intravenous administration of dantrolene alone (1 mg/ kg of body weight, n = 3) significantly decreased pressure in the postprostatic/penile urethral segment, but did not decrease prostatic urethral pressures. Dantrolene in combination with prazosin (0.03 mg/kg, iv) caused a 20% pressure decrease in the prostatic segment (P = 0.060). Preprostatic urethral pressure was not significantly affected by either treatment regimen in the small pool of cats studied. There was no difference in baseline pressures (mm of Hg) in the 3 intraurethral segments of these 6 recently obstructed male cats, compared with historic baseline pressures (mm of Hg) in the 3 intraurethral segments of 28 healthy male cats.

These results indicate that dantrolene and prazosin may be effective in relaxing intraurethral skeletal and smooth musculature in male cats clinically afflicted with obstructive lower urinary tract disease. However, it is not certain that administration of muscle relaxants would facilitate urethral catheterization and removal of the obstruction in male cats with blockage of the lower urinary tract. Strikingly, results of this study suggest that urethral muscle spasm had a minor role in these cats.

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in American Journal of Veterinary Research


Effects of the neuromuscular blocking agent succinylcholine (n = 9), the centrally acting skeletal muscle relaxant diazepam (n = 11), and the direct-acting skeletal muscle relaxant dantrolene sodium (n = 8) on the urethral pressure profile were evaluated in anesthetized, healthy, sexually intact, adult male cats. Intravenous administration of succinylcholine (0.075 mg/kg of body weight) significantly decreased mean absolute pressure in the prostatic and post-prostatic/penile intraurethral segments by −9.5 and −6.5 mm of Hg, respectively (P = 0.0002 and P = 0.0006, respectively). Dantrolene (1.0 mg/kg, iv) significantly decreased mean prostatic and postprostatic/penile intraurethral segmental pressures by −3.5 and −2.8 mm of Hg, respectively (P = 0.005 and P = 0.0181, respectively). Diazepam (0.8 mg/kg, iv) did not significantly alter mean intraurethral segmental pressures. None of the drugs caused a change in segmental lengths of the urethra. These results indicate that skeletal muscle makes a substantial contribution to intraurethral tone in anesthetized, healthy, sexually intact male cats and that skeletal muscle relaxation may be successful in reducing prostatic and post-prostatic/penile urethral segmental tone in male cats. These results also suggest that dantrolene sodium may be valuable for the pharmacologic management of urethral disorders in male cats.

Free access
in American Journal of Veterinary Research