Journal of veterinary pharmacology and therapeutics最新文献

Levetiracetam (LEV) is an anti-epileptic drug used extra-label in dogs. Commercially available extended-release formulations (LEV-ER), administered twice daily, cannot be crushed or split, limiting their use in small dogs. A compounded LEV-ER formulation (PO-COMP) can purportedly be partitioned without loss of extended-release properties. The aims of this study were to establish the pharmacokinetic parameters of PO-COMP, divided at the tablet score, and determine the bioequivalence of partitioned PO-COMP to an intact commercially available Food and Drug Administration-approved human oral generic formulation of LEV-ER (PO-COMM). In a randomized crossover design, 12 healthy dogs received a single IV dose (30 mg/kg) of IV-COMM, a single oral dose (500 mg) of intact PO-COMM, or a single oral dose (500 mg) of partitioned PO-COMP and underwent serial measurement of plasma LEV concentrations over 24 h. PO-COMP was bioequivalent to PO-COMM using the 90% confidence interval method for maximum concentration (-3.2% difference [CI -7.4% to -1.1%]) and area under the curve (-14.4% difference [CI -17.8% to 10.8%]). PO-COMP may improve medication adherence and seizure control relative to immediate-release LEV, which requires three times daily dosing. Efficacy studies of PO-COMP are warranted.

Sea turtles face various threats to survival, primarily due to human activities, such as bycatch, vessel strikes, pollution, and climate change. Many of these activities can lead to illness or injuries, increasing the risk of infection. Treating infections appropriately and effectively requires knowledge of antimicrobial properties and their ability to eradicate microbes without harm to the sea turtle. Robust pharmacokinetic studies, therefore, are important for appropriate dosing. Herein, we review the studies detailing the pharmacokinetic properties of antimicrobials in sea turtles conducted to date.

Salbutamol is a short-acting and selective beta-2 adrenergic agonist. Inhaled (IH) administration of salbutamol is widely used to control lower respiratory tract disease in horses. Here, we estimated the pharmacokinetic parameters of salbutamol after a single intravenous (IV) or IH administration in six horses, and we statistically analysed the detection times with various dosing regimens. Plasma and urine concentrations of salbutamol were measured by liquid chromatography-tandem mass spectrometry, and data were modelled by using a nonlinear mixed effect model followed by Monte Carlo simulation (MCS). With IH salbutamol, the maximum plasma concentration was 0.12 ± 0.06 ng/mL at 0.29 ± 0.17 h after administration. Typical values were, for clearance, 1.53 L/kg/h; distribution volume at steady state, 5.43 L/kg; terminal half-life, 6.06 h; IH bioavailability, 19.0%; and urine to plasma ratio, 2057. Statistically estimated 95th percentile detection times in the urine at levels below the international screening limit (0.5 ng/mL) proposed by the International Federation of Horseracing Authorities, as simulated in 5000 horses by MCS, were 44 h after 1.6 μg/kg q 24 and 54 h after 1.6 μg/kg q 4 h over a 3-day IH administration period.

Abomasal ulcers are a challenge in animal farming, affecting health, welfare, and productivity. Omeprazole's (OPZ) efficacy in treating these ulcers is known, but data on its pharmacokinetics (PK) in adult goats and sheep are lacking. The purpose of this research was to investigate and contrast OPZ's PK in these animals following a single intravenous (IV, 1 mg/kg) and subcutaneous (SC, 2 mg/kg) doses. Sheep and goats had similar exposure levels for all administration routes, with no significant AUC_(0-∞)D variations. Half-life was short in both species (sheep: 0.20 h; goats: 0.31 h). Goats had a higher volume of distribution after IV administration. Clearance was rapid, and extraction ratio values were high for both goats and sheep (43% and 30%, respectively). SC administration showed similarities in C_max and T_max values between species. Both goats and sheep had high bioavailability (about 80%) levels and comparable mean absorption times (MAT). Despite some PK parameters' variances, systemic exposure to OPZ is similar in sheep and goats. SC administration's high bioavailability suggests it as a convenient field application route. Further investigations are needed to understand OPZ's effectiveness in small ruminants with abomasal ulcers and improve dosing regimens for clinical use.

Parasitic infections in dairy cattle reduce herd immunity, milk production, and conception rates. This leads to higher production costs, compromised animal welfare, and increased interest in extralabel drug use. The extralabel use of anthelmintics poses food safety risks for consumers since appropriate withdrawal intervals in milk have yet to be established. Although topical eprinomectin has no milk withdrawal time, more research is needed to determine the residues present in milk after subcutaneous administration. This study aimed to characterize the pharmacokinetics of injectable eprinomectin in dry dairy cows. We hypothesized that, when given at the labeled dose, eprinomectin residues in dry dairy cattle would be below the FDA milk tolerance at the onset of lactation. Plasma was collected daily from 13 mature dairy cattle for 7 days postadministration, followed by periodic samples for 90 days. After calving, milk was collected daily until 90 days. Eprinomectin concentrations were measured using HPLC-fluorescence detection. The maximum eprinomectin concentration in plasma and milk was approximately 36 ng/mL 43 h after administration and 3 ng/mL at the onset of lactation, respectively. The low eprinomectin levels in milk collected from these lactating dairy cattle suggest that administering eprinomectin at dry-off is unlikely to result in violative residues. However, subcutaneous eprinomectin in lactating dairy cattle would be hard to justify unless there is evidence that the approved topical formulation is clinically ineffective.

Water temperature is a critical environmental parameter that significantly influences fish metabolism. This study assessed the metabolism of florfenicol (FF) in tilapia (Oreochromis niloticus) at water temperatures typical of tropical and subtropical regions. Fish were treated with FF by oral administration of a dose of 10 mg kg^-1 bw for 10 consecutive days. Fish fillet, liver, and kidney were sampled during the treatment phase (1, 5, and 10 days) and posttreatment (1, 2, 3, and 5 days after the last FF administration). FF, florfenicol amine (FFA), monochloro florfenicol (FFCl), and florfenicol alcohol (FFOH) were determined in the sampled tissues using a validated LC-LC-MS/MS method. The highest FF, FFA, and FFOH concentrations were determined on day 5 during the treatment phase. For FF, the concentration order is kidney > liver > fillet, while for the metabolites FFOH and FFA, the order is liver > kidney > fillet. In fillet and liver, the concentrations of FFOH were higher than the FFA concentrations, indicating that FFOH was the primary metabolite in these tissues. FFCl was only quantified at concentrations lower than 90 μg kg^-1 in all tissues. The results indicated that FF can be readily absorbed and rapidly eliminated in tilapia cultivated in warm water environments. This study revealed FFOH as the primary and most persistent metabolite in tilapia farmed in warm water, followed by FFA.

The aim of this study was to determine pharmacokinetics of florfenicol and its metabolite florfenicol amine after a single (30 mg/kg) intravenous (IV) and oral administration of florfenicol in chukar partridges. It also aimed to investigate tissue residue and withdrawal time of florfenicol after multiple-dose (30 mg/kg, every 24 h for 5 days) oral administration. The research was carried out in two stages: pharmacokinetics and residue. Plasma and tissue concentrations of florfenicol and florfenicol amine were determined by HPLC. The elimination half-life of florfenicol was 5.25 h for IV and 5.44 h for oral. The volume of distribution at a steady state and total body clearance of florfenicol were 0.38 L/kg and 0.07 L/h/kg, respectively, after IV administration. The peak plasma concentration and bioavailability for oral administration were 45.26 ± 4.06 and 51.55%, respectively. After multiple-dose oral administration, the highest concentration was detected in the liver (9.21 μg/g) for florfenicol and in the kidney (0.67 μg/g) for florfeniol amine. The calculated withdrawal period of florfenicol was determined as 6, 3, 4, and 5 days for muscle, liver, kidney, and skin + fat, respectively. These data indicate that a 6-day WT after multiple-dose administration of florfenicol in chukar partridges can be considered safe for human consumption.

The aim of this study was to compare the pharmacokinetics of marbofloxacin after intravenous (IV) administration of a single dose of 10 mg/kg to calves of different ages. The study was carried on 1- (n = 6), 2- (n = 6), and 4-month-old (n = 6) Montofon calves. Plasma concentrations of marbofloxacin were measured using HPLC, and pharmacokinetic data were calculated by non-compartmental analysis. The elimination half-life (t_1/2ʎz), volume of distribution at steady state (V_dss), total clearance (Cl_T), and area under the concentration-versus time curve (AUC_0-∞) values of marbofloxacin in 1-month-old calves were 10.62 h, 1.03 L/kg, 0.08 L/h/kg, and 127.90 h*μg/mL, respectively. While the t_1/2ʎz (from 10.62 to 3.36 h) and AUC_0-∞ (from 127.90 to 47.35 h*μg/mL) decreased in parallel with the age of the calves, Cl_T (from 0.08 to 0.21 L/h/kg) increased. The V_dss of marbofloxacin was higher in 1- and 2-month-old calves compared to 4-month-old calves. After IV administration of marbofloxacin at a dose of 10 mg/kg, an ƒAUC_0-24/MIC₉₀ ratio of ≥ 125 was obtained for bacteria with MIC₉₀ values of ≤ 0.60, ≤ 0.39 and ≤ 0.27 μg/mL in 1-, 2-, and 4-month-old calves, respectively. These results show that the antibacterial effect of marbofloxacin, which has concentration-dependent activity, decreases due to age-related pharmacokinetic changes and that the 10 mg/kg dose should be reviewed according to the MIC₉₀ value of the bacteria.