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  • Author or Editor: B. J. Fischer x
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Abstract

Objective—To determine pharmacokinetic parameters and variables, firocoxib concentrations in urine and plasma, urine-to-plasma ratios, and the urine depletion profile of firocoxib and to evaluate whether the pharmacokinetic behavior of firocoxib was governed by linear processes after multiple doses of firocoxib were administered IV and orally.

Animals—6 healthy female horses (5 Paint horses and 1 Quarter Horse) in experiment 1 and 12 healthy male and female horses in experiment 2.

Procedures—In experiment 1, 6 horses were orally administered firocoxib paste once daily for 12 consecutive days, and plasma and urine samples were obtained and analyzed. In a second experiment, 12 horses received IV injections of firocoxib solution once daily for 9 consecutive days, and plasma was obtained and analyzed.

Results—Mean ± SD clearance and steady-state volume of distribution of firocoxib were 40.5 ± 14.7 mL/h/kg and 2.3 ± 0.7 L/kg, respectively. Mean half-life was 44.2 ± 21.6 hours and 36.5 ± 9.5 hours for IV and oral administration, respectively. The urine concentration– time curve decreased in parallel with the plasma concentration-verus-time curve. Renal clearance (0.26 ± 0.09 mL/kg/h) was low, compared with total body clearance, which indicated that the main route of elimination was hepatic clearance.

Conclusions and Clinical Relevance—The pharmacokinetics of firocoxib during prolonged use were determined. Use of plasma or urine to ascertain drug concentrations in horses is scientifically valid because the plasma-to-urine ratio was consistent over time and among horses.

Full access
in American Journal of Veterinary Research

Abstract

Objective

To evaluate benign familial hyperphosphatasemia involving serum alkaline phosphatase (SAP) in pups.

Design

Pups with markedly increased SAP activity were evaluated and compared with unaffected siblings, and with other unaffected Siberian Husky pups from the same colony.

Animals

8 related litters of Siberian Husky pups (n = 56).

Procedure

At ages 11 and 16 weeks, pups were given physical examinations and blood was obtained for hematologic and serum biochemical analyses (including electrolytes and isoenzymes of alkaline phosphatase), ionized calcium concentration, and serum parathyroid hormone concentration. Diet, growth and health performance, skeletal radiographs, and genealogical data also were evaluated.

Results

Of 42 pups tested, 17 had markedly high total SAP values. Mean total SAP activity of affected pups at ages 11 and 16 weeks was over 5 times greater than mean total SAP activity of unaffected siblings and other unaffected Siberian Husky pups of the same age (P <0.001). Clinical, radiologic, and biochemical evaluation of the subjects revealed no other abnormal findings. The source of the increased SAP activity was characterized in 5 affected pups as bone isoenzyme. The mode of inheritance could not be deduced from the data, but the trait clearly is familial and autosomal.

Conclusion

The condition described in the family of Siberian Huskies bears similarity to human benign, persistent, familial hyperphosphatasemia.

Clinical Relevance

Benign familial hyperphosphatasemia should be considered in the differential diagnosis of markedly increased SAP activity in young dogs. (Am J Vet Res 1996; 57:612–617)

Free access
in American Journal of Veterinary Research