Journal of veterinary pharmacology and therapeutics最新文献

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.

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.

Uterine vascular alterations take place in pyometra bitches speculatively influenced by prostaglandin and nitric oxide pathways. However, no causative effect of nitric oxide on endometrial vascularization was proved elsewhere for medically treated pyometra bitches. This study aimed to identify the main in situ uterine artery vasodilation pathway in pyometra bitches medically treated with antigestagen solely or coupled with prostaglandin. Pyometra bitches were enrolled into groups: Ovariohysterectomy at diagnosis (Control-OHE; n = 7), Antigestagen (10 mg/kg aglepristone on Days 1, 2, and 8 after diagnosis; n = 5), and Antigestagen + luteolytic (aglepristone plus 1 μg/kg of cloprostenol from Days 1–7; n = 5). Treated bitches were ovariohysterectomized after 8 days of treatment. Uterine artery fragments from all bitches were collected for tissue nitric oxide and prostaglandin E₂ assays. Control-OHE group had lower uterine artery concentration of nitric oxide compared to treated bitches (Antigestagen and Antigestagen + luteolytic groups). No significant difference was verified between the medical treated groups. Uterine artery concentration of prostaglandin E₂ was not different between control and treated bitches, as well as between both treated groups. In conclusion, nitric oxide and prostaglandin E₂ are not directly involved in vascular modulation of the uterine artery, albeit pyometra medical treatment influences nitric oxide concentration in the uterine artery.

Flunixin's pharmacokinetics, bioavailability, and plasma protein binding were examined in rainbow trout. The experiment involved 252 rainbow trout (Oncorhynchus mykiss) maintained at 12 ± 0.6°C. Flunixin was administered to rainbow trout via intravascular (IV), intramuscular (IM), and oral routes at a dosage of 2.2 mg/kg. Plasma samples were collected at times 0 (control), 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, and 96 h. High-pressure liquid chromatography-ultraviolet was employed to quantify flunixin concentrations. The elimination half-life (t_1/2ʎz) for flunixin was 8.37 h for IV, 8.68 h for IM, and 8.76 h for oral. The t_1/2ʎz was similar between administration groups. The volume of distribution at a steady state and total body clearance were 55.81 mL/kg and 6.83 mL/h/kg, respectively, after IV administration. The mean peak plasma concentration was 6.24 ± 0.41 μg/mL at 4 h for oral administration and 13.98 ± 0.86 μg/mL at 2 h for IM administration. The in vitro protein binding ratio of flunixin in rainbow trout plasma was 96.34 ± 2.29%. The bioavailability of flunixin after oral (25.74%) administration was lower than that after IM (66.70%) administration. Thus, developing an oral pharmaceutical formulation that can be administered with feed and has high bioavailability could enhance the therapeutic effect.