Objective—To determine whether older, otherwise healthy, client-owned dogs were deficient in glutathione or cysteine, compared with young healthy pet dogs.
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.
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.
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. (J Am Vet
Med Assoc 2000;217:200–204)
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.
12 healthy employee- and student-owned dogs and blood samples from 2 other healthy untreated dogs and 2 healthy untreated cats.
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.
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.
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.
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
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
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
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
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
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;
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.
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.