Objectives—To measure serum polymyxin B concentration after single and repeated IV infusions in horses.
Animals—5 healthy horses.
Procedures—In study 1, 1 mg (6,000 U) of polymyxin B/kg was given IV and blood samples were collected for 24 hours. In study 2, 1 mg of polymyxin B/kg was given IV every 8 hours for 5 treatments and blood samples were collected until 24 hours after the last dose. Polymyxin B concentration was measured as the ability to suppress nitrite production by murine macrophages stimulated with lipopolysaccharide and interferon-α. Urine was collected prior to the first drug infusion and 24 hours after the fifth drug infusion for determination of urinary γ-glutamyl transferase (GGT)to-creatinine ratios.
Results—In study 1, mean ± SEM maximal serum polymyxin B concentration was 2.93 ± 0.38 μg/mL. Polymyxin B was undetectable 18 hours after infusion. In study 2, maximal polymyxin B concentrations after the first and fifth doses were 2.98 ± 0.81 μg/mL and 1.91 ± 0.50 μg/mL, respectively. Mean trough concentration for all doses was 0.22 ± 0.01 μg/mL. A significant effect of repeated administration on peak and trough serum concentration was not detected. Urine GGT-to-creatinine ratios were not affected by polymyxin B administration.
Conclusions and Clinical Relevance—Polymyxin B given as multiple infusions to healthy horses by use of this protocol did not accumulate in the vascular compartment and appeared safe. Results support repeated IV use of 1 mg of polymyxin B/kg at 8-hour intervals as treatment for endotoxemia.
OBJECTIVE To evaluate the effectiveness and safety of dipyrone to control pyrexia in horses with naturally occurring disease under field conditions.
ANIMALS 138 horses with pyrexia and various infections evaluated at 14 veterinary sites in 12 states.
PROCEDURES In the first (effectiveness) phase of this 2-phase study, horses were randomly assigned 3:1 to receive 1 dose of dipyrone (30 mg/kg [13.6 mg/lb], IV) or an equivalent amount of placebo. Effectiveness was defined as a decrease in rectal temperature ≥ 1.1°C (2°F), compared with the pretreatment value, or a rectal temperature of ≤ 38.3°C (101.0°F) 6 hours after treatment administration. Horses deemed to have an appropriate reduction in rectal temperature (regardless of treatment group) by 6 hours were immediately entered into the safety phase of the study, in which dipyrone was administered IV at 30 mg/kg between 0 and 8 times up to every 8 hours on an as-needed basis, as determined by the clinical investigators. Horses were monitored throughout for adverse events.
RESULTS A significantly greater proportion of dipyrone-treated horses (76/99 [77%]) had an effective treatment response than did placebo-treated horses (6/31 [19%]). Posttreatment adverse events were mild and transient. No differences in types or prevalence of gastrointestinal adverse events were evident between treatment groups.
CONCLUSIONS AND CLINICAL RELEVANCE Dipyrone was effective in controlling pyrexia by 6 hours after IV administration of a single 30-mg/kg dose in a large proportion of treated horses. Adverse effects were minimal.
To perform lipidomic analysis of surfactant and plasma from asthmatic and healthy horses.
30 horses with clinical signs of asthma and 30 age-matched control horses.
Detailed history, physical examination, CBC, and bronchoalveolar lavage fluid (BALF) cytologies were obtained. Asthmatic horses were grouped based on their BALF inflammatory profile: severe equine asthma (SEA), mild equine asthma with neutrophilic airway inflammation (MEA-N), or mild equine asthma with eosinophilic airway inflammation (MEA-E). Each asthma group was assigned its own age-matched control group. Lipidomic analysis was completed on surfactant and plasma. Surfactant protein D (SP-D) concentrations were measured in serum and BALF.
SEA surfactant was characterized by a phospholipid deficit and altered composition (increased ceramides, decreased phosphatidylglycerol, and increased cyclic phosphatidic acid [cPA]). In comparison, MEA-N surfactant only had a decrease in select phosphatidylglycerol species and increased cPA levels. The plasma lipidomic profile was significantly different in all asthma groups compared to controls. Specifically, all groups had increased plasma phytoceramide. SEA horses had increased plasma cPA and diacylglycerol whereas MEA-N horses only had increased cPA. MEA-E horses had increases in select ceramides and dihydrocermides. Only SEA horses had significantly increased serum SP-D concentrations.
The most significant surfactant alterations were present in SEA (altered phospholipid content and composition); only mild changes were observed in MEA-N horses. The plasma lipidomic profile was significantly altered in all groups of asthmatic horses and differed among groups. Data from a larger population of asthmatic horses are needed to assess implications for diagnosis, prognosis, and treatment.