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

Background Acetaminophen has been used clinically in horses alone or combined with traditional non‐steroidal anti‐inflammatory drugs for treatment of musculoskeletal pain in horses. Objectives To determine the pharmacokinetics and efficacy of acetaminophen at two doses in horses with mechanically induced lameness compared with phenylbutazone or placebo control. Study design In vivo experiment. Methods Nine healthy mares with mechanical lameness induced via a reversible sole pressure horseshoe model were treated with acetaminophen (20 mg/kg PO; A20), acetaminophen (30 mg/kg PO; A30), phenylbutazone (2.2 mg/kg, PO; PB) and oral placebo (C) in a randomised four‐way Latin square model. Plasma concentrations for A20 and A30 were analysed via LC‐MS/MS and noncompartmental pharmacokinetic analysis. Heart rate and heart rate variability were measured using a portable telemetry. Lameness was scored by three blinded boarded equine surgeons using the AAEP and 10‐point scales. Results Mean maximum plasma concentration (Cmax) for A20 was 20.01 μg/ml within 0.66 h (Tmax) after administration; The mean Cmax for A30 was 30.02 μg/ml with a Tmax of 0.43 h. Post‐treatment heart rate for A30 was significantly lower than A20 at 1 and 7 h; lower than PB at 2, 3, 4.5 and 7 h; lower than C at 2, 3.5, 4.5, 6, 7 and 8 h. 10‐point Lameness scores were significantly improved for A30 than C at 2 and 4 h post‐treatment; PB was significantly improved than C at 8 h post treatment. There were no significant differences in lameness between A20, A30 and PB. Main limitations Small sample size, lack of objective lameness measurement. Conclusions Acetaminophen at 30 mg/kg produced a more rapid improvement in lameness scores and heart rate compared with other treatments in this model. Further evaluation of the pharmacokinetics and safety of repeated oral dosing of acetaminophen at 30 mg/kg is needed to determine clinical utility.

BackgroundAcetaminophen is used clinically in horses with musculoskeletal pain; however, no studies have been performed in horses with chronic lameness.ObjectivesTo determine the pharmacokinetics, safety and efficacy of chronic dosing of acetaminophen in horses with naturally occurring chronic lameness.Study designLongitudinal.MethodsTwelve adult horses with chronic lameness were treated with acetaminophen (30 mg/kg PO) every 12 h for 21 days. Plasma concentrations of acetaminophen were analysed on days 7 and 21 via LC–MS/MS and noncompartmental pharmacokinetic analysis. Lameness was evaluated by body‐mounted inertial sensor (BMIS) and 10‐point subjective lameness score on day 21 and compared to untreated baseline evaluation on day 35. Clinicopathological analysis (n = 12), hepatic biopsy (n = 6) and gastroscopy (n = 6) were evaluated on days −1 and 22.ResultsMaximum plasma acetaminophen concentration (Cmax) was 20.83 ± 10.25 μg/mL at time (Tmax) 0.40 ± 0.22 h on day 7. The Cmax on day 21 was 17.33 ± 6.91 μg/mL with a Tmax of 0.67 ± 0.26 h. Subjective lameness scores significantly improved at 2 and 4 h post‐treatment; Significant percent improvement was detected in PDmax for horses with hindlimb lameness at 1, 2 and 8 h post‐treatment. There were no significant differences in gastroscopy or hepatic biopsy scores between days −1 and 22.Main limitationsSmall sample size, multi‐limb lameness of varying severity and aetiology, lack of intermediary lameness evaluation.ConclusionsIn horses with naturally occurring chronic lameness, acetaminophen at 30 mg/kg produced a transient improvement in subjective lameness and BMIS evaluation. Acetaminophen may not be effective as a monotherapy. Acetaminophen was safe following 21 days of 30 mg/kg PO every 12 h, with no evidence of clinically significant changes in clinicopathological analysis, hepatic biopsy or gastric ulceration scores.

Antimicrobial-resistant bacteria cause at least 700,000 human deaths per year according to the World Health Organization [1]. The veterinary field remains a relatively minor contributor to the development of antimicrobial resistance, and significant morbidity and mortality associated with antimicrobial resistance remains relatively limited in companion and food animals. However, the risk of antimicrobial-resistant determinants travelling among bacteria, animals and humans through the food chain, direct contact and environmental contamination has made the issue of judicious antimicrobial use in the veterinary field a trending topic both among lawmakers and human healthcare professionals. Reliable estimates for equine morbidity and mortality relating to infection with antimicrobial-resistant bacteria are not yet available. However, cases doubtless occur and the most significant threat to both human and equine populations is multidrug-resistant (MDR) pathogens, including methicillin resistant Staphylococcus aureus (MRSA), extended spectrum betalactamase (ESBL) producing Escherichia coli, MDR Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecium, and rising MDR strains of Salmonella spp. and Clostridium difficile. Veterinarians and their staff carry a higher risk of MRSA colonisation compared to the general population, and nosocomial MRSA infections have been reported in equine hospitals resulting in patient morbidity and significant financial losses [2]. In an analysis of 12,695 antibiograms in France between 2012 and 2016, the highest proportion (22.5%) of MDR-resistant isolates was S. aureus [3]. Carriage and isolation of ESBL E. coli strains that are resistant to all available antimicrobial classes has increased markedly in horses, and are being seen as a rising cause of nosocomial disease in equine hospitals [2]. In a sampling of healthy adult horses at 41 premises in France in 2015, 44% of horses sampled shed MDR-resistant E. coli, with 29% of premises shedding ESBL isolates [4]. Resistance to even 'reserved' classes of antimicrobials has been reported in equine and canine Salmonella isolates, such as the fluoroquinolone-resistant serovar ST198 as well as ESBL and ceftiofur-resistant strains [2]. Macrolide and rifampicin-resistant strains of R. equi have been demonstrated in farms in the United States, and an increasing prevalence has been noted in Kentucky over the period of 2007-2017 compared with the period 1995-2006 [5]. Antimicrobial use is critical to the practice of veterinary medicine and safeguarding animal welfare; however, inappropriate antimicrobial use in equine and companion animal practice may lead the industry to face legislative regulations on par with food animal practices. The World Health Organization has identified five classes of antimicrobials, later generation cephalosporins, glycopeptides, macrolides, polymyxins and quinolones, as being critically important, and therefore reserved, antimicrobials in human medicine [1]. In a recent review of prescribing behaviour of three '...

No abstract