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

An abdominal aortic aneurysm (AAA) is a potentially fatal cardiovascular disease with multifactorial development and progression. Two preclinical models of the disease (elastase perfusion and angiotensin II infusion in apolipoprotein-E-deficient animals) have been developed to study the disease during its initiation and progression. To date, most studies have used ex vivo methods to examine disease characteristics such as expanded aortic diameter or analytic methods to look at circulating biomarkers. Herein, we provide evidence from in vivo ultrasound studies of the temporal changes occurring in biomechanical parameters and macromolecules of the aortic wall in each model. We present findings from 28-day studies in elastase-perfused rats and AngII apoE−/− mice. While each model develops AAAs specific to their induction method, they both share characteristics with human aneurysms, such as marked changes in vessel strain and blood flow velocity. Histology and nonlinear microscopy confirmed that both elastin and collagen, both important extracellular matrix molecules, are similarly affected in their levels and spatial distribution. Future studies could make use of the differences between these models in order to investigate mechanisms of disease progression or evaluate potential AAA treatments.

Objective-To determine whether a limited sampling time method based on serum iohexol clearance (Cl(iohexol)) would yield estimates of glomerular filtration rate (GFR) in clinically normal horses similar to those for plasma creatinine clearance (Cl(creatinine)). Animals-10 clinically normal adult horses. Procedures-A bolus of iohexol (150 mg/kg) was administered IV, and serum samples were obtained 5, 20, 40, 60, 120, 240, and 360 minutes after injection. Urinary clearance of exogenous creatinine was measured during three 20-minute periods. The GFR determined by use of serum Cl(iohexol) and plasma Cl(creatinine) was compared with limits of agreement plots. Results-Values obtained for plasma Cl(creatinine) ranged from 1.68 to 2.69 mL/min/kg (mean, 2.11 mL/min/kg). Mean serum Cl(iohexol) was 2.38 mL/min/kg (range, 1.95 to 3.33 mL/min/kg). Limits of agreement plots indicated good agreement between the methods. Conclusions and Clinical Relevance-Use of serum Cl(iohexol) yielded estimates of GFR in clinically normal adult horses similar to those for plasma Cl(creatinine). This study was the first step in the evaluation of the use of serum Cl(iohexol) for estimating GFR in adult horses.

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