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  • Author or Editor: Karen R. Dyer x
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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

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

Bilateral midbody hemimandibular osteotomies were performed between premolars 3 and 4 in 18 adult dogs. Hemimandibles were repaired by use of monocortically applied bone plates (n = 6), an interdental fixator composed of an Erich arch bar and acrylic (n = 6), or a type I external skeletal fixator (n = 6). At the immediate postoperative evaluation, hemimandibles stabilized with interdental fixators had an osteotomy gap distance (mean ± SEM, 1.6 ± 0.2 mm) that was significantly (P < 0.05) greater than for hemimandibles stabilized with external skeletal fixators (1.2 ± 0.3 mm). Osteotomy gap distance of hemimandibles stabilized with external skeletal fixators (1.5 ± 0.2 mm) was significantly (P < 0.05) greater at weeks 4 (1.1 ± 0.2 mm) and 8 (0.8 ± 0.3 mm) after surgery than the osteotomy gap distance of hemimandibles stabilized by application of bone plates. By week 16, significant differences in osteotomy gap distance were not detected between groups. Immediately after surgery, mandibular alignment measurements were not significantly different for dogs with bone plates (0.3 ± 0.1 mm), interdental fixators (0.3 ± 0.1 mm), and external skeletal fixators (0.9 ± 0.5 mm). Mandibular alignment scores were not significantly different between treatment groups during the remaining postoperative period. Occlusal measurements were not significantly different between evaluations performed before surgery and 16 weeks after surgery, regardless of treatment group. Radiographic evidence of healing in hemimandibles stabilized with external skeletal fixators was significantly (P < 0.05) less at 4 and 8 weeks, compared with hemimandibles stabilized with bone plates and interdental fixators; however, radiographic evidence of bone healing was not significantly different between fixation groups at 16 weeks. Radiographic evidence of implant loosening was seen in 1 of 12 (8%) hemimandibles receiving bone plates, 1 of 12 (8%) hemimandibles receiving interdental fixators, and 4 of 12 (33%) hemimandibles receiving external skeletal fixators. Periosteotomy callus was radiographically evident in 11 of 18 (61%) hemimandibles at 4 and 8 weeks only, but significant differences in periosteotomy callus surface area were not detected between groups. Of 24 hemimandibles stabilized with interdental and external skeletal fixators, 22 (92%) had callus formation that progressively matured into trabecular bone by 16 weeks. At 4 weeks, bone healing characterization scores of hemimandibles stabilized with bone plates were significantly (P < 0.05) less than (ie, had greater stability) bone healing characterization scores of hemimandibles stabilized with interdental and external skeletal fixators, but at 8 and 16 weeks, bone healing characterization scores between treatment groups were not significantly different. Histopathologic or radiographic evaluation did not reveal evidence of pulp disease or pathologic changes of teeth, which would have been associated with root resection at the osteotomy site, application of acrylic to the crown surface, or placement of external fixator pins and cortical screws. On the basis of the fact that the dogs appeared clinically normal and were able to masticate, analgesics were discontinued by 24 hours after surgery. Analysis of data indicated that an interdental fixator composed of an Erich arch bar and acrylic may be a viable method for fracture repair of mandibles.

Free access
in Journal of the American Veterinary Medical Association