Journal of veterinary pharmacology and therapeutics最新文献

Rifampin is an enigma among antimicrobials. Blood and tissue compartment concentrations are a “moving target” along the treatment course due to the complex pharmacodynamic interactions within the body. Rifampin concomitant therapies are for the prevention and treatment of Rhodococcus equi infection in foals, for nearly 40 years. The necessity of rifampin concomitant therapies is based on beliefs that both antimicrobials (e.g., rifampin plus macrolide) penetrate into pulmonary abscesses and intracellular compartments above R. equi minimum inhibitory concentrations (MICs), as well as better efficacy, compared with other approaches, and limiting the rate of antimicrobial resistance to either single agent. However, rifampin acts as a perpetrator drug for many co-administered drugs. This critical review evaluates the available evidence for rifampin use in foals with R. equi , concerning pharmacokinetic/pharmacodynamic characteristics of rifampin in foals, in vitro microbiological studies and selection of antimicrobial resistance, as well as an analysis of randomized clinical trials. Rifampin is a nuclear pregnane X receptor activator, which results in strong negative drug interactions towards itself and other drugs, for drug-absorption routes either by upregulation of presystemic elimination mechanisms (e.g., intestinal and hepatic CYP3A4), or functional drug-absorption carriers (e.g., intestinal P-glycoprotein) and/or inhibition of intestinal and/or hepatic drug-uptake carriers (e.g., OATP1B1, OATP2B1, MRP2). Chronic rifampin administration results in decreases in the serum and target site/s concentrations of many parent drugs, including itself. Rifampin concomitant therapies do not demonstrate a significant advantage over monotherapy with macrolides, in randomized controlled blinded and double-blinded clinical trials for subclinical, and mild-to-moderate bronchopneumonia in foals with pulmonary abscesses, regardless of initial pulmonary abscess score. Efficacy of rifampin concomitant therapies for severe Rhodococcus equi pneumonia has not been fully investigated, but there is sufficient accumulated evidence in foals to raise major concerns about the incorrect use of rifampin in equine medicine. These concerns include rifampin as a bacteriostatic antibiotic against R. equi , with changing pharmacokinetics during treatment that decreases parent/coparent concentrations as well as the risk of selecting for multi-resistant R. equi .

There is a shifting public perception of animal welfare that has increased demand for establishing pain management strategies in livestock. Gabapentin is often utilized in practice to mitigate neuropathic pain. However, there is little pharmacokinetic information to guide its use in goats. The objectives of this study were to describe the pharmacokinetics of oral gabapentin in goats given as a single dose (SD) and multidose (MD) regimen, as well as to document any adverse effects after administration. Six healthy adult goats were administered 15 mg/kg of gabapentin orally once for the SD trial, and every 12 h for 6 doses for the MD trial. Plasma samples were collected and analyzed via reversed-phase high-performance liquid chromatography. After SD administration, maximum plasma concentration, time to maximum concentration, and elimination half-life were: 3.22 μg/mL; 4.49 h; and 8.15 h, respectively. After MD administration, maximum plasma concentration and time to maximum concentration were: 4.56 μg/mL and 2.24 h. Accumulation ratio (R) was 1.66 ± 0.81 when comparing the MD AUC12_h to the SD AUC12_h. Clinicians should be aware of the potential for increased accumulation ratio with multiple dosing strategies.

The objective of this investigation was to ascertain the impact of gender on the pharmacokinetics of meloxicam in sheep. The research was carried out on six female and six male Romanov sheep. Meloxicam was administered intravenously to sheep at a dose of 1 mg/kg. To determine the change in meloxicam concentration with time, blood samples were collected at 17 different time points up to 120 h after administration. Meloxicam concentrations in plasma samples were determined using high-performance liquid chromatography. The pharmacokinetics of meloxicam in sheep was found to differ according to gender. The values of total clearance (Cl_T), volume of distribution at steady state (V_dss), and elimination half-life (t_1/2λz) of meloxicam in female sheep were 4.51 ± 0.56 mL/h/kg, 69.18 ± 6.68 mL/kg, and 11.96 ± 0.33 h, respectively. Compared to female sheep, Cl_T and V_dss were increased, and t_1/2λz was decreased in male sheep. Plasma concentration and area under the curve of meloxicam were higher in female sheep. The findings of this study indicate that meloxicam's pharmacokinetics are not uniform across genders in Romanov sheep, with notable variations in plasma concentration, clearance, and half-life. These variations emphasize the importance of considering gender in the pharmacotherapy of sheep, potentially guiding clinicians in adjusting dosages for optimal therapeutic outcomes and maintaining food safety standards.

Reproducibility and replicability of study results are crucial for advancing scientific knowledge. However, achieving these goals is often challenging, which can compromise the credibility of research and incur immeasurable costs for the progression of science. Despite efforts to standardize reporting with guidelines, the description of statistical methodology in manuscripts often remains insufficient, limiting the possibility of replicating scientific studies. A thorough, transparent, and complete report of statistical methods is essential for understanding study results and mimicking statistical strategies implemented in previous studies. This review outlines the key statistical reporting elements required to replicate statistical methods in most current veterinary pharmacology studies. It also offers a protocol for statistical reporting to aid in manuscript preparation and to assist trialists and editors in the collective strive for advancing veterinary pharmacology research.

Persistence of antimicrobial drugs (AMDs) administered to poultry is longer in feathers than in edible tissues. Hence, poultry feathers are a suitable matrix to investigate historical exposure contributing to antimicrobial resistance, since current detection methods are either non-specific or highly technical and costly. Here we present an analysis of the performance of lateral flow test (LFT) panels in the detection of five AMD classes, namely sulfonamides, tetracyclines, beta-lactams, quinolones, and aminoglycosides, on chicken feather samples. The limit of detection (LOD) of eight AMD substances was determined between 4.7 μg/kg for enrofloxacin and 700 μg/kg for streptomycin. The performance of feather LFT was evaluated for four AMD classes against the reference method (LC–MS/MS). From 79 samples collected from the field, LFT test specificity ranged from 0.63 (quinolones) to 0.95 (tetracyclines). Test sensitivity ranged from 0.15 (beta-lactams) to 0.78 (quinolones and tetracyclines). LFT testing had the greatest discriminatory power for tetracyclines (specificity 0.95 and sensitivity 0.78). LFT had similar test characteristics for sulfonamides and quinolones and performed poorly for beta-lactams. Poor recovery rates (< 15%) were observed in neomycin, kanamycin, and ampicillin. These methods are suitable for preliminarily screening tetracyclines, sulfonamides, and quinolones, with recommendations for further extraction protocols.

The pharmacokinetics and plasma protein binding of amoxicillin in cats has not been thoroughly investigated. In a single-group sequential designed experimental study, amoxicillin was administered to six healthy cats intravenously, orally, and subcutaneously. Repeated blood samples were drawn after each administration, and amoxicillin concentrations were determined using High Performance Liquid Chromatography coupled to Triple Quadrupole Mass Spectrometry. Plasma amoxicillin data were subjected to population pharmacokinetic analysis, and pharmacokinetic parameters were estimated. The population clearance was 0.18 L/h∙kg, the volume of the central compartment was 0.12 L/kg, the highly perfused compartment was 0.009 L/kg, and the poorly perfused compartment was 0.002 L/kg. The bioavailability was 33% and 69% after oral and subcutaneous administration, respectively. After subcutaneous administration of a slow-release formulation, there was absorption rate-limited pharmacokinetics. The plasma protein binding was 0%–24%. The results increase the understanding of the amoxicillin pharmacokinetics in cats. Further studies combining the results with pharmacodynamic data and in silico simulations are warranted.