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- Author or Editor: Lauren A. Trepanier x
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Abstract
Objective—To determine whether older, otherwise healthy, client-owned dogs were deficient in glutathione or cysteine, compared with young healthy pet dogs.
Design—Cross-sectional study.
Animals—35 healthy dogs between 7 and 14 years old (older dogs) and 26 healthy dogs between 1 and 3 years old (young dogs).
Procedures—In all dogs, erythrocyte reduced glutathione concentration and plasma cysteine concentration were determined by means of high-performance liquid chromatography.
Results—Median erythrocyte reduced glutathione and plasma cysteine concentrations were not significantly different between young (1.7 mM and 8.3 μM, respectively) and older (1.7 mM and 7.6 μM, respectively) dogs. Significant differences were also not identified when values for young dogs were compared with values for only those dogs ≥ 11 years old. Similarly, no differences were found between males and females overall or between males and females within age groups, although most dogs were neutered.
Conclusions and Clinical Relevance—Results suggested that otherwise healthy older pet dogs fed a variety of commercial diets do not have deficiencies in glutathione or cysteine, compared with younger dogs. Findings do not support the routine empirical use of antioxidant supplements, such as precursors of glutathione, to treat presumed circulating antioxidant deficiencies in older healthy dogs.
Abstract
Objective—To determine whether there are therapeutically relevant changes in serum phenobarbital concentrations throughout a daily dosing interval in epileptic dogs receiving phenobarbital for ≥ 3 weeks.
Design—Prospective study.
Animals—33 epileptic dogs receiving phenobarbital.
Procedure—Serum phenobarbital concentrations were measured at 0 hour (trough), 3 hours, and 6 hours after oral administration of phenobarbital in epileptic dogs that had received phenobarbital twice daily for a minimum of 3 weeks. For each dog, trough, 3-hour, and 6-hour serum phenobarbital concentrations were evaluated to determine whether they were within the same therapeutic category (lower, middle, or upper end of the therapeutic range of 15 to 45 µg/ml), or whether there was a > 30% change in serum concentrations throughout the day.
Results—Ninety-one percent (30/33) of dogs had trough, 3-hour, and 6-hour serum phenobarbital concentrations in the same therapeutic category. Only 9% (3/33) of dogs had trough, 3-hour, and 6-hour serum concentrations in different therapeutic categories with a > 30% change in concentrations throughout the day. Significant differences were not detected among mean serum phenobarbital concentrations when comparing the trough, 3-hour, and 6- hour samples for all dogs.
Conclusions and Clinical Relevance—There is no
therapeutically relevant change in serum phenobarbital
concentrations throughout a daily dosing interval in
most epileptic dogs. Therefore, timing is not important
when collecting blood samples to measure
serum phenobarbital concentrations in most epileptic
dogs treated long-term with phenobarbital. (
Abstract
OBJECTIVE
To determine whether metronidazole (MTZ), at recommended therapeutic dosages in dogs, induces peripheral blood cell (PMBC) genotoxicity, using the γ-H2AX assay as a sensitive measure of DNA breaks. The secondary aim was to assess dose-dependent genotoxicity in vitro in dog and cat PBMCs exposed to increasing MTZ concentrations.
ANIMALS
12 healthy employee- and student-owned dogs and blood samples from 2 other healthy untreated dogs and 2 healthy untreated cats.
PROCEDURES
Screened dogs were randomized to receive lower-dose MTZ (7.5 mg/kg, PO, q 12 h) or higher-dose MTZ (20 mg/kg, PO, q 12 h) for 7 days. Blood was drawn at baseline, after the 1 week of treatment, and after a 1-week washout, for DNA damage assessment and serum MTZ concentration measurements. For in vitro studies, PBMCs from untreated healthy dogs and cats were exposed to 0 to 500 μg/mL MTZ.
RESULTS
No dogs showed a significant increase in DNA damage at these MTZ dosages for 1 week. The highest serum MTZ concentration observed 1 hour after dosing was 36 μg/mL. In vitro, MTZ led to a significant increase in DNA damage at 100 μg/mL in both canine and feline PBMCs.
CLINICAL RELEVANCE
Although MTZ was not significantly genotoxic in vivo in the healthy dogs in this study, MTZ was significantly genotoxic to canine PBMCs in vitro at 3-fold higher concentrations than those documented in vivo. The safety of MTZ in clinically ill dogs, which may have impaired MTZ clearance or DNA repair, should be assessed next.
Abstract
Objective—To determine the pharmacokinetics of ceftazidime following subcutaneous administration and continuous IV infusion to healthy dogs and to determine the minimum inhibitory concentration (MIC) of ceftazidime for clinical isolates of Pseudomonas aeruginosa.
Animals—10 healthy adult dogs.
Procedure—MIC of ceftazidime for 101 clinical isolates of P aeruginosa was determined in vitro. Serum concentrations of ceftazidime were determined following subcutaneous administration of ceftazidime (30 mg/kg of body weight) to 5 dogs and continuous IV infusion of ceftazidime (loading dose, 4.4 mg/kg; infusion rate, 4.1 mg/kg/h) for 36 hours to 5 dogs.
Results—The MIC of ceftazidime for P aeruginosa was ≤ 8 µg/ml; all isolates were considered susceptible. Following SC administration of ceftazidime, mean β disappearance half-life was 0.8 hours, and mean serum ceftazidime concentration exceeded the MIC for P aeruginosa for only 4.3 hours. Two dogs had gastrointestinal tract effects. Mean serum ceftazidime concentration exceeded 16 µg/ml during continuous IV infusion. None of the dogs developed adverse effects.
Conclusions and Clinical Relevance—Administration of ceftazidime subcutaneously (30 mg/kg, q 4 h) or as a constant IV infusion (loading dose, 4.4 mg/kg; rate, 4.1 mg/kg/h) would maintain serum ceftazidime concentrations above the MIC determined for 101 clinical isolates of P aeruginosa. Use of these dosages may be appropriate for treatment of dogs with infections caused by P aeruginosa. (Am J Vet Res 2000;61:1204–1208)
Abstract
Objective—To determine whether once daily administration of methimazole was as effective and safe as twice daily administration in cats with hyperthyroidism.
Design—Randomized, nonblinded, clinical trial.
Animals—40 cats with newly diagnosed hyperthyroidism.
Procedure—Cats were randomly assigned to receive 5 mg of methimazole, PO, once daily (n = 25) or 2.5 mg of methimazole, PO, twice daily (15). A complete physical examination, including measurement of body weight; CBC; serum biochemical analyses, including measurement of serum thyroxine concentration; and urinalysis were performed, and blood pressure was measured before and 2 and 4 weeks after initiation of treatment.
Results—Serum thyroxine concentration was significantly higher in cats given methimazole once daily, compared with cats given methimazole twice daily, 2 weeks (3.7 vs 2.0 μg/dL) and 4 weeks (3.2 vs 1.7 μg/dL) after initiation of treatment. In addition, the proportion of cats that were euthyroid after 2 weeks of treatment was lower for cats receiving methimazole once daily (54%) than for cats receiving methimazole twice daily (87%). Percentages of cats with adverse effects (primarily gastrointestinal tract upset and facial pruritus) were not significantly different between groups.
Conclusions and Clinical Relevance—Results suggest that once daily administration of methimazole was not as effective as twice daily administration in cats with hyperthyroidism and cannot be recommended for routine use. (J Am Vet Med Assoc 2003; 222:954–958)
Abstract
OBJECTIVE
To characterize the biochemical, functional, and histopathologic changes associated with lomustine-induced liver injury in dogs.
ANIMALS
I0 healthy purpose-bred sexually intact female hounds.
PROCEDURES
Dogs were randomly assigned to receive lomustine (approx 75 mg/m2, PO, q 21 d for 5 doses) alone (n = 5) or with prednisone (approx 1.5 mg/kg, PO, q 24 h for 12 weeks; 5). For each dog, a CBC, serum biochemical analysis, liver function testing, urinalysis, and ultrasonographic examination of the liver with acquisition of liver biopsy specimens were performed before and at predetermined times during and after lomustine administration. Results were compared between dogs that did and did not receive prednisone.
RESULTS
7 of the I0 dogs developed clinical signs of liver failure. For all dogs, serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities, bile acid concentrations, and liver histologic score increased and hepatic reduced glutathione content decreased over time. Peak serum ALT (r = 0.79) and ALP (r = 0.90) activities and bile acid concentration (r = 0.68) were positively correlated with the final histologic score. Prednisone did not appear to have a protective effect on histologic score.
CONCLUSIONS AND CLINICAL RELEVANCE
In dogs, liver enzyme activities, particularly ALT and ALP activities, should be closely monitored during lomustine treatment and acute increases in those activities may warrant discontinuation of lomustine to mitigate liver injury. Nonspecific ultrasonographic findings and abnormal increases in liver function tests were not detected until the onset of clinical liver failure. Glutathione depletion may have a role in lomustine-induced hepatopathy and warrants further investigation.
