Summary Background There are no published studies on the pharmacokinetics of acetaminophen at the dosage used clinically (20 mg/kg), nor has the safety of multiple doses in horses been investigated. Objective Define the pharmacokinetic parameters of oral acetaminophen at 20 mg/kg in adult horses as a single dose, and twice daily for 14 days to assess the safety of multiple dosing. Study design Pharmacokinetic study, multiple dose safety study. Methods Eight healthy Thoroughbred geldings were given acetaminophen (20 mg/kg; 500 mg tablets) orally as a single dose followed by doses every 12 h for 14 days. Serial blood samples were collected for determination of plasma acetaminophen concentrations using high performance liquid chromatography with ultraviolet detection. Serum biochemical analysis, gastroscopy and liver biopsy were examined during the safety study. Results Following a single dose, mean maximum concentration (Cmax) was 16.61 μg/mL at 1.35 h (Tmax), and drug concentration was below the lower limit of detection in most horses by 24 h. Elimination half‐life (T1/2) was 2.78 h. No significant accumulation was noted following multiple doses. Average Cmax of acetaminophen following multiple oral dosing was 15.85 μg/mL, with a Tmax of 0.99 h and T1/2 of 4 h. Serum activities of sorbitol dehydrogenase were significantly decreased and total bilirubin concentrations were significantly increased following the last dose. No statistically significant changes were noted in gastroscopy scores. Main limitations Only one dose level (20 mg/kg) was studied, sample size was small and only a single breed and sex was used, with no pretreatment liver biopsies. Conclusion This study described the pharmacokinetics of acetaminophen following single and multiple 20 mg/kg oral doses in adult horses and demonstrated the safety of acetaminophen with multiple oral dosing over 14 days. The summary is available in Portuguese – see Supporting information

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Dogs participating in endurance exercise, including herding, hunting and racing have a greater energy requirement and may be more susceptible to nutrient depletion, electrolyte imbalance and metabolic stress. The objective of the present study was to investigate the acute response to unstructured mixed exercise in American Foxhounds fed a nutrient-fortified endurance diet. Thirty-nine adult Foxhound dogs (median age: 5·0, range: 2–10 years and median body weight (BW): 36·4, range: 24·9–49·5 kg) were allotted to a standard performance diet (Control) or nutrient-fortified endurance diet for adult dogs (Test). Dogs were balanced by sex, age, BW and athletic performance between diets. All male dogs were intact, whereas all the female dogs were spayed. After 80 d on diet, blood samples were collected via jugular puncture at baseline (0 h), and at 3 and 25 h post-exercise (mean: 17·7 (sem 0·92) km run over 2–3 h). Plasma taurine concentration and complete amino acid (AA) profile, serum chemistry and creatine kinase were measured. Serum chemistry profile remained within normal ranges throughout the study. A significant (P < 0·05) diet by time interaction was observed for calcium, alkaline phosphatase and most AA. Plasma taurine and most essential AA were increased (P < 0·05) after exercise and remained greater (P < 0·05) in dogs fed the Test diet, including the branched-chain AA (isoleucine, leucine and valine). Creatine kinase increased (P = 0·01) after 3 h and returned to baseline after 25 h post-exercise, but was not altered by diet. These data indicate that dogs undergoing a moderate bout of exercise did not suffer from electrolyte imbalance, and that a nutrient-fortified diet resulted in greater plasma taurine and essential AA concentrations.

The objective of the present study was to evaluate the changes in blood metabolites, AA profile, and oxidative stress markers in American Foxhound dogs fed a nutrient-fortified endurance diet while undergoing unstructured endurance exercise over several months. Thirty-six adult American Foxhound dogs (mean age: 4.5, range 2 to 10 yr and mean BW: 34.7, range: 23.1 to 46.9 kg) were selected to participate in the study. Prior to the study, all dogs consumed a commercial diet for 16 wk. After collecting baseline blood samples, dogs were assigned to a standard commercial performance diet (control) or a nutrient-fortified dog food (test). Dogs were balanced by gender, age, body weight, and athletic performance between diets. During the study, dogs underwent 78 bouts of exercise, with approximately 22 km/bout. Blood samples were collected after 40, 75, 138, and 201 d on study (October 2012 to March 2013). All blood metabolites were similar at baseline and serum chemistry profile remained within normal ranges throughout the study. Over time, plasma taurine and vitamin E concentrations decreased (P < 0.05) in dogs fed the control diet but were maintained or increased (P < 0.05) in dogs fed the treatment diet. Also, plasma creatinine and triglycerides were lower (P < 0.05) and blood phosphorus and alkaline phosphatase were higher (P < 0.05) in dogs fed the treatment diet. Vitamin E and taurine status of dogs appear to be affected by extended endurance exercise. These data suggest dogs undergoing endurance exercise may benefit from supplementation of vitamin E and taurine to minimize oxidation and maintain taurine status.