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in Journal of the American Veterinary Medical Association
in Journal of the American Veterinary Medical Association
in Journal of the American Veterinary Medical Association

Abstract

Objectives—To measure urine concentrations of sulfated glycosaminoglycans (GAGs), determine optimal storage conditions for urine samples, establish a reference range, and determine whether there is correlation between 24-hour total urine GAG excretion and the GAG-to-creatinine ratio (GCR).

Animals—14 healthy adult dogs.

Procedure—Single urine sample GAG concentrations and GCRs were measured in samples collected from 14 healthy dogs at the start of the 24-hour collection period. Twenty-four–hour total urine GAG excretions were determined from urine collected during a 24-hour period in the same 14 dogs. Total sulfated GAG concentrations were also measured in urine from these dogs after the urine had been stored at 4°C and -20°C for 1, 7, and 30 days.

Results—Urine GAG concentrations were not significantly different from baseline values after urine was stored at 4°C for up to 1 day and -20°C for up to 30 days. Neither single urine sample GAG concentration (R , 0.422) nor GCR (R , 0.084) was an adequate predictor of 24-hour total urine GAG excretion.

Conclusions and Clinical Relevance—Results of this study provide data that can be used to establish a reference range for 24-hour total urine GAG excretion in dogs and adequate conditions for sample storage. Contrary to findings in humans, there was no significant linear correlation between 24-hour total urine GAG excretion and single urine sample GCR in dogs, limiting clinical use of the single urine sample test.

Full access
in American Journal of Veterinary Research

SUMMARY

Clorazepate dipotassium was administered orally to 8 healthy dogs at a dosage of 2 mg/kg of body weight, q 12 h, for 21 days. Serum disposition of nordiazepam, the principle metabolite of clorazepate, was determined after the first and last dose of clorazepate. Disposition variables were analyzed by use of model-independent pharmacokinetics by the predictive equations method and the trapezoidal rule method. Complete blood counts, serum chemical analyses, and urinalyses were performed before administration of clorazepate and at 10 and 21 days after administration of clorazepate.

Maximal nordiazepam concentrations ranged from 446 to 1,542 ng/ml (814 ± 334 ng/ml), at 59 to 180 minutes (97.9 ± 42.0 minutes) after a single oral dose of clorazepate. Maximal nordiazepam concentrations ranged from 927 to 1,460 ng/ml (1,308 ± 187.6 ng/ml), at 120 to 239 minutes (153 ± 57.9 minutes) after multiple oral doses of clorazepate. Serum disposition was significantly altered after multiple doses of clorazepate. Using data determined by the predictive equations method, the mean residence time after multiple doses (712 ± 214 minutes) was longer (P < 0.05) than after a single dose (527 ± 95.8 minutes). Oral volume of distribution after multiple doses of clorazepate (1.76 ± 0.647 L/kg) was smaller (P < 0.02) than after a single dose (3.18 ± 1.52 L/kg). Oral clearance after multiple doses of clorazepate (3.09 ± 0.726 ml/min/kg) was less (P < 0.001) than after a single dose (6.54 ± 2.15 ml/min/kg). Absorption half-life after multiple doses (72 minutes) was longer (P < 0.01) than after a single dose (33 minutes). The elimination half-life after a single dose (284 minutes) was not significantly different after multiple doses (355 minutes).

Significant changes (P < 0.05) in serum chemical values after multiple doses of clorazepate included decreased concentrations of albumin, total protein, and calcium and increased concentrations of urea nitrogen and glucose. Serum activities of alkaline phosphatase and alanine transaminase increased after multiple doses of clorazepate. Significant changes (P < 0.05) in the hemogram included increased total wbc count, segmented neutrophils, lymphocytes, and eosinophils. Urine pH after multiple doses (5.88 ± 0.641) was lower (P < 0.01) than after a single dose (7.44 ± 1.29). All changes in laboratory values remained within our reference ranges.

Mild sedation and ataxia developed in only 1 dog after the first dose of clorazepate. These effects were transient and did not redevelop with additional dosing.

An oral clorazepate dosage of 2 mg/kg, q 12 h, maintains serum nordiazepam concentrations considered to be therapeutic in human beings (500 to 1,900 ng/ml).

Free access
in American Journal of Veterinary Research

Summary

The effects of short-term phenobarbital administration were evaluated in 6 adult mixed-breed dogs that received phenobarbital (5 mg/kg of body weight, PO, q 12 h) for 8 consecutive weeks. Six additional dogs served as untreated controls. At 2-week intervals, endogenous adrenocorticotropic hormone (ACTH) concentration and cortisol concentration before and 2 hours after administration of porcine aqueous ACTH (2.2 IU/kg, M) were measured. By means of oneway ANOVA, we were not able to detect a significant (P ≥ 0.05) difference in endogenous ACTH concentration and cortisol concentration before and after exogenous ACTH administration within groups over time or between groups at any time.

To evaluate effects of long-term phenobarbital administration, sera and plasma were collected from 5 epileptic dogs that had received phenobarbital for > 2 years and had serum phenobarbital concentrations > 20 μg/dl. Endogenous ACTH concentration and cortisol concentration, before and after administration of ACTH, were within established reference ranges for all 5 dogs.

Together, these results suggest that phenobarbital administration alone does not affect endogenous ACTH concentration or response to exogenous ACTH administration in dogs, and that these may be valid screening tests for hyperadrenocorticism in most dogs receiving phenobarbital.

Free access
in Journal of the American Veterinary Medical Association

Summary

We determined whether administration of cisplatin in hypertonic saline solution would prevent significant decrease in renal function, as measured by exogenous creatinine clearance, in healthy dogs. A single dose of cisplatin (70 mg/m2 of body surface) was mixed in 3% saline solution and was infused IV (6.5 ml/kg of body weight) over a 20-minute period to 6 healthy dogs. Exogenous creatinine clearance was determined prior to treatment of dogs with cisplatin and again on days 3 and 21 after administration of cisplatin. All 6 dogs vomited at least once within 12 hours of treatment with cisplatin; however, clinically important changes in appetite, body weight, or hydration status were not apparent during the 21-day study. Although mean values for exogenous creatinine clearance decreased from baseline on days 3 and 21, changes were not significantly different. Renal histologic lesions included mild, chronic, lympho-plasmacytic interstitial nephritis in 5 dogs, and presumably, were unrelated to treatment with cisplatin. Mild renal tubular atrophy (n = 2) and tubular necrosis (n = 1) may have developed secondary to treatment with cisplatin. Results of this study indicated that administration of a single dose of cisplatin in 3% saline solution to healthy dogs was not associated with significant decrease in glomerular filtration rate. This is a convenient protocol for administering cisplatin; however, additional study is required before it can be recommended for clinical patients, especially those with preexisting renal disease or those receiving multiple doses of cisplatin.

Free access
in American Journal of Veterinary Research

Summary

The disposition of clorazepate, a benzodiazepine anticonvulsant, was determined in dogs after administration of a single oral dose of clorazepate (2 mg/kg of body weight) and after oral administration of clorazepate (2 mg/kg, q 12 h) concurrently with phenobarbital (5 mg/kg, q 12 h) for 44 consecutive days. Serum concentrations of nordiazepam, the active metabolite of clorazepate, were measured. After a single oral dose of clorazepate, maximal nordiazepam concentrations ranged from 569.6 to 1,387.9 ng/ml (mean, 880.2 ± 248.9 ng/ml) and were detected 16.8 to 131.4 minutes (mean, 85.2 ± 36 minutes) after dosing. After administration of phenobarbital for 44 consecutive days, maximal nordiazepam concentrations were significantly (P < 0.01) lower, ranging from 209.6 to 698.5 ng/ml (mean, 399.3 ± 155.6 ng/ml) at 68.4 to 145.8 minutes (mean, 93 ± 25.8 minutes) after dosing. Mean area under the curve (AUC) on day 1 (mean, 3.37 ± 0.598 ng·min/ml) was significantly (P < 0.001) greater than AUC on day 44 (1.66 ± 0.308 ng·min/ml). Oral clearance was significantly (P < 0.01) greater on day 44 (12.44 ± 2.55 ml/min/kg), compared with that on day 1 (6.16 ± 1.35 ml/min/kg). Values for area under the first moment curve, oral volume of distribution, mean residence time, and elimination half-life were not significantly altered by concurrent administration of phenobarbital.

Administration of phenobarbital altered the disposition of clorazepate such that the amount of nordiazepam in circulation during each dose interval was significantly reduced. Adequate control of seizures in epileptic dogs, therefore, may require higher dosages of clorazepate when it is coadministered with phenobarbital.

Free access
in American Journal of Veterinary Research