If time-dependent pharmacodynamics apply, IVRLP with 500 mg of meropenem may be ineffective and would likely promote resistance.

No abstract

Horse diets are often supplemented with dietary fat to increase caloric intake, and although the effects of fat on fiber digestibility have been studied, this research has not included the use of cannulated subjects. A decrease in fiber digestibility due to fat would be detrimental to equine performance, and thus, the current study utilized cannulated ponies as an equine model for any effects on fiber digestibility due to supplemental dietary fat on a forage diet. Five Shetland/hackney pony mares with an ileal and cecal cannula were fed hay, 2 kg/d alfalfa pellets and vegetable oil at 0, 5, 10 or 15% of total diet. Experimental diets were fed twice a day at 0600 and 1600 hours. Ponies were allowed a 14-d diet adjustment period, after which ileal and cecal cannula samples and fecal grab samples were collected at 1, 3 and 5 d post diet adjustment. On day 1, samples were taken at 0, 90, 180, 270 min and 7 and 10 h. Day 3 samples were taken at 30, 120, and 210 min, and 5 and 8 h. On d 5 samples were taken at 60, 150, and 240 min and 6 and 9 h post feeding. Samples were analyzed for crude protein, fat, acid-detergent fiber, acid-detergent lignin, and apparent digestibility of dry matter, crude protein, fat, and acid-detergent fiber. No effects were found on fiber digestibility due to fat supplementation up to 15% of the total diet in a pony model (P > 0.1). Results indicated that equine diets could be supplemented with up to 15% of fat in the form of vegetable oil to increase digestible energy with no negative impact on fiber digestibility.

Objective To determine synovial butorphanol concentrations and mechanical nociceptive threshold (MNT) changes after butorphanol intravenous regional limb perfusion (IVRLP). Study design Experimental Animals Six adult horses. Methods Cephalic IVRLP was performed with 10 mg butorphanol in sedated horses with a wide rubber tourniquet and a total volume of 30 mL. Radiocarpal synovial fluid and serum concentrations along with MNT were evaluated prior to and 0.5, 1, 2, 4, and 6 hours after IVRLP. Butorphanol concentrations were determined with liquid chromatography coupled to tandem mass spectrometry positive electrospray ionization. Results Butorphanol concentrations reached mean (SD) peak concentrations of 9.47 ng/mL (±12.00) in synovial fluid and 3.89 ng/mL (3.29) in serum 30 minutes after IVRLP. Concentrations remained above baseline for 4 hours in synovial fluid (P ≤ .017) and for 2 hours in serum (P ≤ .016). The only difference in MNT was detected 1 hour after IVRLP, when MNT were higher in controls than in treated horses (P = .047). Conclusion Butorphanol IVRLP seemed well tolerated and resulted in measurable levels of butorphanol in the radiocarpal synovial fluid of five of six horses. Clinical significance Intravenous regional limb perfusion appears to be a viable alternative to administer butorphanol, but additional investigation is required to evaluate the dose and local concentrations required for analgesia.

The objective of this study was to determine the pharmacokinetics of meropenem in horses after intravenous (IV) administration. A single IV dose of meropenem was administered to six adult horses at 10 mg/kg. Plasma and synovial fluid samples were collected for 6 hr following administration. Meropenem concentrations were determined by bioassay. Plasma and synovial fluid data were analyzed by compartmental and noncompartmental pharmacokinetic methods. Mean ± SD values for elimination half‐life, volume of distribution at steady‐state, and clearance after IV administration for plasma samples were 0.78 ± 0.176 hr, 136.1 ± 19.69 ml/kg, and 165.2 ± 29.72 ml hr‐1 kg−1, respectively. Meropenem in synovial fluid had a slower elimination than plasma with a terminal half‐life of 2.4 ± 1.16 hr. Plasma protein binding was estimated at 11%. Based on a 3‐compartment open pharmacokinetic model of simultaneously fit plasma and synovial fluid, dosage simulations were performed. An intermittent dosage of meropenem at 5 mg/kg IV every 8 hr or a constant rate IV infusion at 0.5 mg/kg per hour should maintain adequate time above the MIC target of 1 μg/ml. Carbapenems are antibiotics of last resort in humans and should only be used in horses when no other antimicrobial would likely be effective.