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  • Author or Editor: Nancy J. Szabo x
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Abstract

Objective—To determine pharmacokinetics of azathioprine (AZA) and clinical, hematologic, and serologic effects of IV and oral administration of AZA in horses.

Animals—6 horses.

Procedure—In study phase 1, a single dose of AZA was administered IV (1.5 mg/kg) or orally (3.0 mg/kg) to 6 horses, with at least 1 week between treatments. Blood samples were collected for AZA and 6-mercaptopurine (6-MP) analysis 1 hour before and at predetermined time points up to 4 hours after AZA administration. In study phase 2, AZA was administered orally (3 mg/kg) every 24 hours for 30 days and then every 48 hours for 30 days. Throughout study phase 2, blood samples were collected for CBC determination and serum biochemical analysis.

Results—Plasma concentrations of AZA and its metabolite, 6-MP, decreased rapidly from plasma following IV administration of AZA, consistent with the short mean elimination half-life of 1.8 minutes. Oral bioavailability of AZA was low, ranging from 1% to 7%. No horses had abnormalities on CBC determination or serum biochemical analysis, other than 1 horse that was lymphopenic on day 5 and 26 of daily treatment. This horse developed facial alopecia from which 1 colony of a Trichophyton sp was cultured; alopecia resolved within 1 month after the study ended.

Conclusions and Clinical Relevance—Overall, no adverse effects were observed with long-term oral administration of AZA to horses, although 1 horse did have possible evidence of immunosuppression with chronic treatment. Further investigation of the clinical efficacy of AZA in the treatment of autoimmune diseases in horses is warranted. (Am J Vet Res 2005;66:1578–1583)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine and compare the effects of caffeine and doxapram on cardiorespiratory variables in foals during isoflurane-induced respiratory acidosis.

Animals—6 clinically normal foals (1 to 3 days old).

Procedures—At intervals of ≥ 24 hours, foals received each of 3 IV treatments while in a steady state of hypercapnia induced by isoflurane anesthesia (mean ± SD, 1.4 ± 0.3% endtidal isoflurane concentration). After assessment of baseline cardiorespiratory variables, a low dose of the treatment was administered and variables were reassessed; a high dose was then administered, and variables were again assessed. Sequential low- and high-dose treatments included doxapram (loading dose of 0.5 mg/kg, followed by a 20-minute infusion at 0.03 mg/kg/min and then 0.08 mg/kg/min), caffeine (5 mg/kg and 10 mg/kg), and saline (0.9% NaCl) solution (equivalent volumes).

Results—Administration of doxapram at both infusion rates resulted in a significant increase in respiratory rate, minute ventilation, arterial blood pH, PaO 2, and arterial blood pressure. These variables were also significantly higher during doxapram administration than during caffeine or saline solution administration. There was a significant dose-dependent decrease in PaCO 2 and arterial bicarbonate concentration during doxapram treatment. In contrast, PaCO 2 increased from baseline values after administration of saline solution or caffeine. The PaCO 2 value was significantly lower during doxapram treatment than it was during caffeine or saline solution treatment.

Conclusions and Clinical Relevance—Results indicated that doxapram restored ventilation in a dose-dependent manner in neonatal foals with isoflurane-induced hypercapnia. The effects of caffeine on respiratory function were indistinguishable from those of saline solution.

Full access
in American Journal of Veterinary Research