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The safety of synthetic levothyroxine sodium tablets (Thyro-Tabs® Canine; LLOYD, Inc.) in dogs was evaluated in a randomized, sham-dose controlled, parallel-group study. Young, healthy, euthyroid Beagle dogs were randomized into four groups (four females and four males per group) and received single daily doses of 0×, 2× (0.044 mg/kg), 6× (0.132 mg/kg), or 10× (0.22 mg/kg) the labeled starting dose of 0.022 mg kg-1 day-1 for 182 days. Every 2 weeks, physical examinations, electrocardiology examinations, and sample collections for thyroid panel, hematology, serum biochemistry, coagulation panel, and urinalysis were performed. At the end of the study, the dogs were euthanized and full necropsies performed. The most overt finding was the expected dose-dependent increase in serum concentrations of total and free thyroxine with dose-dependent suppression of the hypothalamic-pituitary-thyroid axis as evidenced by decreased serum thyroid-stimulating hormone concentrations, decreased thyroid+parathyroid/body weight ratios, and a trend for decreased pituitary weight/brain weight ratios. Clinical signs of thyrotoxicosis (excitation, tachypnea, tachycardia) in the treated dogs were sporadic with no dose-response relationship. Other findings statistically associated with levothyroxine treatment were generally mild and not clinically important. In summary, doses of levothyroxine sodium up to 10× the labeled starting dose were well tolerated in healthy dogs.

To test effectiveness of IV administration of tolazoline hydrochloride in reversing xylazine hydrochloride-induced sedation in calves.Prospective study.12 female and 12 male Friesian-cross calves from 5 to 7 months old.Calves were assigned to 1 of 4 treatment groups. Calves were given xylazine (0.3 mg/kg [0.14 mg/lb] of body weight, IM). Twenty minutes later, calves were treated with saline (0.9% NaCl) solution (1 ml/50 kg [1 ml/110 lb], IV) or tolazoline (1, 2, or 4 mg/kg [0.45, 0.9, or 1.8 mg/lb], IV). Behavioral and physiologic measurements included elapsed time from xylazine administration to recumbency, arousal and standing times after reversal drug administration, heart rate, and respiratory rate.Mean (+/- SD) recumbency time for all calves was 5.4 +/- 1.8 minutes. Compared with administration of saline solution, all 3 doses of tolazoline significantly decreased arousal and standing times. Mean arousal time for calves receiving saline solution was 27.8 +/- 11.5 minutes. Administration of tolazoline at 1, 2, and 4 mg/kg resulted in mean arousal times of 4.7 +/- 3.8, 0.9 +/- 0.5, and 0.7 +/- 0.3 minutes, respectively. Mean standing time for calves receiving saline solution was 38.8 +/- 2.8 minutes. Administration of tolazoline at 1, 2, and 4 mg/kg resulted in mean standing times of 14.0 +/- 11.0, 3.0 +/- 1.2, and 2.4 +/- 1.1 minutes, respectively.For routine use, tolazoline doses of 1 to 2 mg/kg should suffice. In cattle, IV administration of tolazoline reverses pharmacologic effects of xylazine, thereby hastening recovery from xylazine-induced sedation.

Twenty healthy ponies were given i.v. 1.1 mg/kg of xylazine from 2 manufacturers and the pharmacokinetic parameters calculated from the disposition curves. The disposition curves for the 2 commercial preparations were not different. Yohimbine, an antagonist of the pharmacologic effects produced by xylazine, did not alter the disposition of xylazine in the plasma. A single i.v. bolus of xylazine was completely described in 17 of 20 animals by the biexponential equation: Cp = 1.30e(-0.3955t) + 0.58e(-0.033t) where Cp represents the concentration of xylazine in the plasma at time t (min). The t1/2 beta was 75 +/- 13 min and whole body clearance was 18.9 +/- 1.5 (ml/min.kg).