Safety of orally administered, USP-compliant levothyroxine sodium tablets in dogs.

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.

On the duration of spatial fluency measures.

Various measures of spatial fluency have been developed and have been shown to be sensitive to right frontal lobe dysfunction. Patients with diffuse cerebral injuries (traumatic brain injury) also show impaired performance. Administration times for these tests range from three to five minutes. It is well known that longer tests provide more reliable data. In the present study, the base rates of unique designs and perseverative errors on the Five-Point Test were examined minute-by-minute for ten minutes, in a sample of healthy young adults (n=80). Contrasts between each minute showed significant decreases in number of unique designs to the ninth minute (significant at p<.001). Contrasts between each minute revealed significant increases (significant at p<.00l) in percentage of perseverative errors to the eighth minute. Data demonstrating the progressive decrease of unique designs and progressive increase of perseverative errors as a function of time have important implications for clinical practice. Optimal administration time is considered in the context of clinicians' objectives.