OBJECTIVE To investigate the effect of high doses of orally administered levothyroxine sodium (LT4) on serum concentrations of triiodothyronine (T3) and thyroxine (T4) in euthyroid horses. ANIMALS 12 healthy adult horses. PROCEDURES 10 horses initially received water (vehicle) or 240 mg (5X treatment) or 480 mg (10× treatment) of LT4, and blood samples were collected at baseline (0 hours) and 0.5, 1, 2, 4, 6, 8, 10, 12, 18, 24, 48, 72, 96, and 120 hours after treatment to measure serum T3 and T4 concentrations. Three horses then received 480 mg of LT4 for 14 days, and T4 concentration was measured on days 0, 14, 21, 28, and 35. Changes in T3 and T4 concentrations were compared over time and among treatments. RESULTS One-time administration of LT4 resulted in variable but significant increases in both T3 and T4 concentrations for up to 120 hours; however, T3 and T4 concentrations rarely exceeded reference intervals with either treatment. Prolonged administration of 480 mg of LT4 resulted in a 15-fold increase in T4 concentration after 14 days, but concentration returned to day 0 values within 21 days after LT4 administration was discontinued. CONCLUSIONS AND CLINICAL RELEVANCE In euthyroid horses, administration of a high dose of LT4 resulted in mild increases in thyroid hormone concentrations; however, prolonged administration of high doses of LT4 resulted in markedly increased thyroid hormone concentrations that returned to pretreatment values within 3 weeks after discontinuation of LT4 administration. These results indicated complex kinetics of LT4 and suggested a possible saturation of T4 excretion in euthyroid horses.
Objectives The aim of this study was to determine famciclovir content (strength) in compounded formulations and to determine if potency changed over time. Methods Four concentrations of oral oil suspension in three distinct flavors, three concentrations of oral paste, three chew treats and 62.5 mg tablets from one compounding pharmacy were evaluated for famciclovir content. Specific sample preparation procedures were used for each drug formulation prior to determination of famciclovir content through mass spectrometry tandem liquid chromatography. Analysis was performed on arrival from the compounder and on days 7, 14, 28, 56 and 120. Samples were run in triplicate and concentration determined by comparison with a standard curve. Content was considered appropriate if within 90–110% of the labeled concentration. Results On arrival from the compounding pharmacy, 5/12 oral oil suspensions of varying concentrations were <90% of the labeled concentration and 3/3 oral pastes were >110%. Famciclovir content in oil suspensions ranged from 72% to 118% of the label value while oral pastes ranged from 95% to 202% of the label concentration over the 120 study days, and all concentrations varied in an unpredictable fashion. Tablets contained 90–110% of the labeled value throughout the study period. Chew treats could not be successfully analyzed. Conclusions and relevance This study found substantial variation in famciclovir content in the compounded products evaluated, which, in turn, raises concerns that substandard dosing could result in lack of efficacy or a failed treatment trial. Drug toxicity might also be encountered. Veterinarians must be aware that while compounded medications can improve compliance, they might not deliver the drug dose expected.
Background: The use of thyroid supplement is pervasive in athletic horses although its effects on measures of performance are not known.Objectives: One purpose of this study was to determine whether supra-physiologic doses of levothyroxine affect the velocities at which blood lactate was greater than 4 mmol/L (V La4 ) and heart rate was over 150 (V 150 ) and 200 (V 200 ) beats per minute respectively. Additionally, a survey of post-race blood samples was also conducted to determine whether high thyroxine concentrations were common in racehorses. Study design:A randomised, crossover, trial was performed in six healthy Standardbred racehorses.Methods: Study 1: T4 was determined in 50 post-race samples from a single Standardbred meet. Study 2: Research horses were trained to fitness and then randomised to one of three treatments: carrier, 0.1 mg/kg thyroxine or 0.25 mg/kg thyroxine for 2 weeks. Horses completed a standardised exercise treadmill test (SET) to fatigue on the last day of treatment. Serum free and total thyroxine and triiodothyronine were determined on the day of SET testing. Blood lactate and ECG data were collected during the SET at 6, 8, 10, 11, and 12 m/s and during recovery. The effect of treatment and SET on heart rate and blood lactate was examined using generalised linear mixed models. Post hoc analysis was adjusted for multiple comparisons using Tukey's Test. Data were expressed as mean ± standard deviation and P < .05 was considered significant.Results: Study 1: The median T4 value in this population of horses was 2.00 µg/dL (laboratory's normal range 1.5-4.5 µg/dL) and 3 of 50 racehorses had values above the laboratory reference range. Study 2: Levothyroxine at 0.25 mg/kg resulted in higher heart rates during SET (199 ± 30, 223 ± 17 and 239 ± 9 bpm at 6, 8 and 10 m/s respectively) and recovery (144 ± 20 and 119 ± 15 at 5 and 15 min) as compared to placebo (176 ± 18, 203 ± 10 and 219 ± 6 bpm at 6, 8, and10 m/s and 126 ± 5, 102 ± 11 at 5-15 minutes respectively). Three of six horses developed cardiac arrhythmias including atrial fibrillation. Main limitations:A relatively small number of animals were used and a SET is not identical to actual racing conditions.
Veterinary prescriptions are becoming more common in the community-practice setting due to a variety of factors, including cost, availability, convenience and legislation changes. However, veterinary patients are not simply small humans with regards to drug use, and this can be seen in dosages that drastically differ from those used in humans, beyond adjustment for size differences. Therefore, it is important for a pharmacist filling these prescriptions to have an understanding of basic differences regarding drug disposition in veterinary patients as well as factors that may influence toxicity and/or adverse effects. This article also reviews commonly used veterinary drug references that a pharmacist can use in the community-practice setting to aid in review of veterinary prescriptions.
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