Journal of veterinary pharmacology and therapeutics最新文献

The fluoroquinolone antimicrobial agents, enrofloxacin and marbofloxacin, were approved in the United States for cats in 1990 and 2001, respectively. In 2023, revised breakpoints for testing isolates from dogs were published. These canine breakpoints are discordant with the current feline breakpoints. This study was aimed at suggesting new feline breakpoints using a pharmacokinetic-pharmacodynamic (PK-PD) approach and new pharmacokinetic data. The PK-PD derived cutoff values (CO_PD) were compared to microbiologic data available for testing the susceptibility of targeted pathogens since the original approval. Compared to the current Clinical and Laboratory Standards Institute (CLSI) breakpoints for enrofloxacin and marbofloxacin in cats, these revised breakpoints are lower by two dilutions for the Enterobacterales, Pseudomonas aeruginosa, Staphylococcus spp., and Pasteurella multocida. Isolates that may have previously tested susceptible (S) may test resistant (R) using these suggested breakpoints. We also are suggesting a susceptible dose-dependent (SDD) category for testing marbofloxacin against these isolates from cats that allows for a higher dose. These suggested breakpoints may be considered by laboratories, standard-setting organizations, and industry sponsors of these antimicrobials for testing common bacteria isolated from cats.

There has been a growing interest in the use of cannabinoids in horses in recent years. Several studies have reported on the pharmacokinetics of cannabidiol (CBD) in horses. However, cannabidiolic acid (CBDA) has received less attention, despite limited evidence suggesting clinically beneficial effects in other species. Horses were administered 3 mg/kg of CBD, 3 mg/kg of CBDA, and a placebo per os in a crossover design, with a one-week washout period between treatments. Plasma and urine samples were collected and analyzed using ultra high-performance liquid chromatography coupled to tandem mass spectrometric. Observed CBDA plasma concentrations were up to 67 times higher, and the CBDA area under the plasma concentration-time curve was up to 36 times larger than those of CBD. Median terminal half-lives in plasma were 7.8 h for CBD and 5.3 h for CBDA. Both compounds were detectable in plasma for up to 72 h. In urine, CBD and CBDA were detectable for 168 and 72 h, respectively. The results suggest greater intestinal uptake or lower first-pass metabolism/clearance of CBDA compared to CBD. Given the poor oral bioavailability of CBD in horses, CBDA may hold greater clinical relevance. Further studies are needed to elucidate the pharmacokinetics and pharmacodynamics of CBDA in horses.

The purpose of this study was to evaluate the pharmacokinetics of oral (PO) ondansetron compared to intravenous (IV) ondansetron in eight healthy client-owned dogs. Dogs were randomized to one of two protocols in a crossover design, receiving PO or IV ondansetron at a dose of 1 mg/kg on Day 0 and the opposite formulation at an equal dose on Day 7. Plasma was collected at baseline and 1, 2, 4, and 8 h post administration. Ondansetron concentrations were measured utilizing liquid chromatography/mass spectrometry. For IV administration, AUC_0–8h was 1181 ± 619 ng/mL*h, with all dogs having detectable plasma concentrations at all time points. For PO administration, mean C_max was 22 ± 11.3 ng/mL and AUC_0–8h was 61.7 ± 45.4 ng/mL*h, with all dogs having undetectable concentrations at various time points. Oral mean bioavailability was estimated at 5.2% ± 2.1%. Oral bioavailability of ondansetron is very low in healthy dogs, raising concern for the efficacy of ondansetron when given orally at 1 mg/kg. Future studies evaluating pharmacodynamics of ondansetron in nauseous client-owned dogs should be performed to investigate whether plasma drug concentrations are the optimal way to assess the efficacy of oral ondansetron.

Ilunocitinib, a novel Janus kinase inhibitor, is indicated for managing pruritus and skin lesions associated with canine allergic and atopic dermatitis. Pharmacokinetics of ilunocitinib were investigated following single intravenous and oral administrations, both in fed and fasted states. Dose proportionality was assessed using oral doses ranging from 0.4 to 4.0 mg/kg, and multiple dosing was evaluated with daily oral doses of 0.8 mg/kg. Serial blood samples were collected, and plasma concentrations of ilunocitinib were measured using a validated LC–MS/MS method. Pharmacokinetic samples were also collected in field trials. Intravenous administration resulted in low plasma clearance (0.437 L/h/kg), a volume of distribution of 1.58 L/kg, and a terminal half-life of 4.4 h. Oral administration led to rapid absorption (T_max usually ranging between 1 and 4 h) and higher bioavailability in fed dogs (80%) compared to fasted dogs (61%). The prandial effect observed in laboratory studies with single doses was not clinically relevant under field conditions. Exposure increased less than proportionally with increasing doses. No clinically relevant accumulation was observed with 0.8 mg/kg daily dosing. No sex-based differences were observed. Altogether, ilunocitinib pharmacokinetics support a once-daily oral dosing in dogs. Minimal accumulation, also confirmed in long-term studies, further supports the safety of ilunocitinib with a daily dosing regimen.

Prophylactic and perioperative use of antibiotics is common prior to abdominal surgery in cattle for minimizing the risk of postoperative infections. Yet, there is little information on drug concentrations at sites of potential infections following surgical procedures. The objective of this study was to compare the concentrations in the plasma, peritoneal fluid, and interstitial fluid of ampicillin trihydrate in cattle. In a randomized design, ampicillin trihydrate, a β-lactam antibiotic, was administered to 12 healthy Holstein-Friesian steers intraoperatively via intraperitoneal (IP; n = 6) or intramuscular (IM; n = 6) injection in the cervical neck muscles at 11 mg/kg for both groups. For IP administration, ampicillin trihydrate was deposited into the abdominal cavity following an incision in the right paralumbar fossa. Steers in the IM group were administered ampicillin prior to surgical closure. Peritoneal fluid and interstitial fluid were collected using ultrafiltration probes. IP administration achieved higher concentrations in peritoneal fluid as compared to IM administration. Maximum plasma concentrations were significantly higher following IP administration (3.11 ± 2.5 μg/mL; p < 0.004) compared to the IM group (0.05 ± 10.9 μg/mL). Despite high peritoneal fluid concentrations of ampicillin, the variability in critical pharmacokinetic parameters following IP administration raises concerns about its therapeutic reliability. The correlation between intraperitoneal drug concentrations and clinical efficacy warrants further investigation.