Journal of veterinary pharmacology and therapeutics最新文献

Porcine respiratory diseases is a major cause of economic losses in livestock, and ceftiofur is one of the core therapeutic agents for its treatment, but the clinical efficacy can be inconsistent. Therefore, it is necessary to utilize a population pharmacokinetic model to reveal the distribution and metabolic patterns of ceftiofur in pig populations, while also combining Monte Carlo simulation techniques to predict the probability of treatment success under different dosing regimens. To investigate the probability of attaining the pharmacokinetic/pharmacodynamic targets of ceftiofur in pigs infected with different respiratory bacteria, a population pharmacokinetic model for the intramuscular administration of ceftiofur in pigs was developed, and Monte Carlo simulation was performed to analyze the target attainment rate of ceftiofur at different doses. The results showed that the target attainment rate of ceftiofur was 100% for Pasteurella multocida at the dose of 0.5 mg/kg b.w. intramuscularly, 99.9% for Actinobacillus pleuropneumoniae at 1 mg/kg b.w. intramuscularly, 93.4% for Streptococcus suis at 0.5 mg/kg b.w. intramuscularly, and 95.4% for Haemophilus parasuis at 10 mg/kg b.w. intramuscularly. The results indicate that it is crucial to optimize the dosage based on specific infected bacteria to improve the success rate of treatment and extend the clinical application period of ceftiofur.

Trailing endpoints are a recognised challenge in broth microdilution MIC testing, particularly for bacteriostatic agents such as trimethoprim (TMP) and sulphonamides. In this study, we applied a pharmacodynamically guided refinement to determine the MIC of the combination against Staphylococcus pseudintermedius; we did not aim at redefining clinical susceptibility, but at refining MIC determination to better guide pharmacodynamic study design. By providing more reliable thresholds for growth suppression, this approach supports optimisation of PD modelling and may ultimately inform translational applications, such as dose prediction and reducing misclassification in PD contexts. Visual MICs were compared to those derived from log₁₀ changes in CFU/mL over 24 h, using pharmacodynamic thresholds of +2.3 log₁₀ (growth from standard inoculum of 5 × 10⁵ to ~10⁸ CFU/mL, corresponding to visible growth MIC) and 0 log₁₀ change (stationary concentration). Across 10 clinical isolates, visual MICs often underestimated the concentration required to suppress growth by 2-4 fold (more than one dilution step), particularly for sulphonamides. TMP-sulphonamide combinations at a 1:19 ratio showed reduced trailing and closer agreement between visual and count-based MICs, reflecting enhanced bactericidal activity. Time-kill curve experiments anchored on the log₁₀ count-based MIC provided a well-distributed range of PD responses, capturing both suppression and killing more accurately than curves centred on visual MICs. This method supports more rational selection of concentrations for PD studies and may be especially valuable for slow-acting or ratio-sensitive combinations, and has translational value for sulphonamides, such as sulfamethoxazole, used in both human and veterinary medicine.

Whitespotted bamboo sharks (Chiloscyllium plagiosum) are a common species of elasmobranchs housed in zoos and aquaria. Medical concerns like conspecific trauma and bacterial infections commonly lead to the empirical use of antibiotic medications like ceftazidime, despite limited pharmacokinetic studies in elasmobranchs. In this study, 36 whitespotted bamboo sharks were divided into six groups using a population pharmacokinetic design. They were administered a single intramuscular injection of ceftazidime at 20 mg/kg. Blood samples were collected for plasma drug concentration at time points T = 0 and 30 min, and 1, 2, 4, 6, 12, 24, 48, 72, and 96 h post-injection. Samples were analyzed by the Clinical Pharmacology Laboratory in the College of Veterinary Medicine of North Carolina State University using high-pressure liquid chromatography (HPLC) analysis. For at least 96 h, all sharks in the study maintained plasma concentrations of ceftazidime above the MIC of 4 μg/mL, which is considered susceptible when testing isolates from other animals. The long elimination half-time of 84.15 h suggests that recommended dosing intervals may be extended beyond the commonly used 3 days to at least every 96 h.

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.