Plasma disposition of cefoperazone after single intravenous and intramuscular administrations in camels (Camelus dromedarius)

The plasma disposition of cefoperazone was investigated after intravenous (IV) and intramuscular (IM) administrations of 20 mg/kg as a single dose in six camels (Camelus dromedarius) in a crossover design. Blood plasma samples were analysed by high-performance liquid chromatography (HPLC). After IV administration, elimination half-life (t1/2β), volume of distribution at steady state (Vdss), total body clearance (Cltot) and mean residence time (MRT) of cefoperazone were 1.95 h, 0.38 L/kg, 0.17 L/h/kg and 2.16 h, respectively. After IM administration of cefoperazone, peak plasma concentration (Cmax) was 21.95 μg/mL and it was obtained at (tmax) 1.23 h. Absorption half-life (t1/2ab), elimination half-life and mean absorption time were 0.45 h, 2.84 h and 2.07 h, respectively. The bioavailability of cefoperazone was 89.42%. The lack of local reaction or any other adverse effects and the very good bioavailability following IM administration indicate that cefoperazone might be a promising alternative treatment for a variety of infectious diseases in camels

Changes in novel gastrointestinal and renal injury markers in the blood plasma of sheep following increasing intravenous doses of tolfenamic acid

The administration of high doses of non-steroidal anti-inflammatory drugs (NSAID), such as tolfenamic acid (TA), has undesirable effects on different organs. Some novel biomarkers have been reported that can determine the gastrointestinal and renal injury caused by a high dose of NSAIDs or other toxic substances. This study was aimed at determining the changes in gastrointestinal (TFF2 and HYP), renal (NGAL and KIM-1) and cardiac (cTn-I, CK-MB) injury markers after the use of increasing intravenous doses of TA in sheep. TA was administered intravenously to groups of six sheep each, at the dose levels of 0 (Group 0, i.e., G0), 2 (G2), 4 (G4), 8 (G8) and 16 (G16) mg/kg. The concentrations of the studied biomarkers were measured at 3, 9, 18 and 36 h after administration of TA. The TFF2 and NGAL concentrations in G16 were found to be significantly higher (P < 0.05) than in the other groups except for G8 at different sampling times. HYP concentration in G16 was observed to be significantly (P < 0.05) lower than that in all other groups at 36 h. KIM-1 level in G16 was significantly (P < 0.05) higher than in all other groups at different sampling times. An increase in the renal markers, KIM-1 and NGAL, in G8 was observed before any change in plasma creatinine and urea. The cardiac marker cTn-I in G16 was significantly (P < 0.05) higher than in other groups at different sampling times. The results showed that the novel biomarkers (HYP, TFF2, NGAL, and KIM-1) can be used to determine gastric and renal injury in sheep

Pharmacokinetics and Pharmacokinetic/Pharmacodynamic Integration of Enrofloxacin Following Single Oral Administration of Different Doses in Brown Trout (Salmo trutta)

The pharmacokinetic of enrofloxacin was investigated in brown trout (Salmo trutta) following oral administration of 10, 20, and 40 mg/kg doses at 11 ± 1.5 °C. Furthermore, MICs of enrofloxacin against Aeromonas hydrophila and A. sobria were determined. The plasma concentrations of enrofloxacin and ciprofloxacin were determined using HPLC–UV and analyzed by non-compartmental method. Following oral administration at dose of 10 mg/kg, total clearance (CL/F), area under the concentration–time curve (AUC0−∞) and peak plasma concentrations (Cmax) were 41.32 mL/h/kg, 242.02 h*μg/mL and 4.63 μg/mL, respectively. When compared to 10 mg/kg dose, the dose-normalized AUC0–∞ and Cmax were increased by 56.30% and 30.08%, respectively, while CL/F decreased by 38.4% at 40 mg/kg dose, suggesting the non-linearity. Ciprofloxacin was not detected in the all of plasma samples. The MIC values of enrofloxacin were ranged 0.0625–4 μg/mL for A. hydrophila and 0.0625–2 μg/mL for A. sobria. The oral administration of enrofloxacin at 10 (for 192 h) and 20 (for 240 h) mg/kg doses provided the AUC of enrofloxacin equal to 1.23 and 1.96-fold MICs, respectively, for A. hydrophila and A. sobria with the MIC90 values of 1 µg/mL. However, further researches are needed on the PK/PD study of enrofloxacin for the successful treatment of infections caused by A. hydrophila and A. sobria in brown trout

Pharmacokinetics and Bioavailability of Carprofen in Rainbow Trout (Oncorhynchus mykiss) Broodstock

The aim of this study was to determine the pharmacokinetics of carprofen following intravenous (IV), intramuscular (IM) and oral routes to rainbow trout (Oncorhynchus mykiss) broodstock at temperatures of 10 ± 1.5 °C. In this study, thirty-six healthy rainbow trout broodstock (body weight, 1.45 ± 0.30 kg) were used. The plasma concentrations of carprofen were determined using high-performance liquid chromatography and pharmacokinetic parameters were calculated using non-compartmental analysis. Carprofen was measured up to 192 h for IV route and 240 h for IM, and oral routes in plasma. The elimination half-life (t1/2λz) was 30.66, 46.11, and 41.08 h for IV, IM and oral routes, respectively. Carprofen for the IV route showed the total clearance of 0.02 L/h/kg and volume of distribution at steady state of 0.60 L/kg. For IM and oral routes, the peak plasma concentration (Cmax) was 3.96 and 2.52 μg/mL with the time to reach Cmax of 2 and 4 h, respectively. The bioavailability was 121.89% for IM route and 78.66% for oral route. The favorable pharmacokinetic properties such as the good bioavailability and long t1/2λz for IM and oral route of carprofen suggest the possibility of its effective use for the treatment of various conditions in broodstock

Development and Validation of a High-Performance Liquid Chromatography Method for Determination of Cefquinome Concentrations in Sheep Plasma and Its Application to Pharmacokinetic Studies▿

Cefquinome has a broad spectrum of antibacterial activity and was developed especially for use in animals. A simple and sensitive high-performance liquid chromatography (HPLC) method with UV-visible detection for quantification of cefquinome concentrations in sheep plasma was developed and validated. Separation of cefquinome from plasma components was achieved on a Phenomenex Gemini C18 column (250 mm by 4.6 mm; internal diameter [i.d.], 5 μm). The mobile phase consisted of acetonitrile and 0.1% trifluoroacetic acid in water and was delivered at a rate of 0.9 ml/min. A simple and rapid sample preparation involved the addition of methanol to 200 μl of plasma to precipitate plasma proteins followed by direct injection of 50 μl of supernatant into the high-performance liquid chromatography system. The linearity range of the proposed method was 0.02 to 12 μg/ml. The intraday and interday coefficients of variation obtained from cefquinome were less than 5%, and biases ranged from −3.76% to 1.24%. Mean recovery based on low-, medium-, and high-quality control standards ranged between 92.0 and 93.9%. Plasma samples were found to be stable in various storage conditions (freeze-thaw, postpreparative, short-term, and long-term stability). The method described was found to be readily available, practicable, cheap, rapid, sensitive, precise, and accurate. It was successfully applied to the study of the pharmacokinetics of cefquinome in sheep. This method can be very useful and an alternate to performing pharmacokinetic studies in the determination of cefquinome for clinical use

Influences of flunixin and tenoxicam on the pharmacokinetics of florfenicol in lipopolysaccharide-induced endotoxemia

The purpose of this study was to investigate the influences of flunixin (FM) and tenoxicam (TN) on the pharmacokinetics of florfenicol (FF) after coadministration in lipopolysaccharide (LPS)-induced endotoxemic rabbits. Fifteen male rabbits were used in this study. FF (20 mg/kg), FM (2 mg/kg), and TN (1 mg/kg) were coadministered via intravenous injection to the animals. The concentrations of FF were determined by high-performance liquid chromatography with diode-array detection from 0.08 to 12 h in plasma. The plasma concentration-time profile of FF was described using a noncompartmental open model. In this study, terminal half-life, area under the curve, mean residence time, and volume of distribution at steady state were significantly increased, whereas total body clearance was decreased in coadministered groups. In conclusion, FM and TN have effects on the pharmacokinetics of FF in coadministered endotoxemic rabbits. When FF is coadministered with FM and TN, it can be given at a dose of 20 mg/kg b.w. every 8 h for treatment of infections caused by susceptible pathogens with a minimum inhibitory concentration (MIC) of <= 2 mu g/mL or 12 h for treatment of infections caused by susceptible pathogens with MIC of <= 1 mu g/mL in critically ill rabbits. Further studies are necessary to determine variations in dosage regimens

Combined Treatment with Interlukin-1 and Tumor Necrosis Factor-Alpha Antagonists Improve Type 2 Diabetes in Rats

In the present study, combined treatment with etanercept and anakinra were tested in the streptozotocin-induced diabetic rats. Forty male Wistar albino rats were divided into 5 groups; healthy control (HC), diabetic control (DC), diabetic+anakinra (DAT), diabetic+etanercept (DET), and diabetic+etanercept+anakinra (DEAT). HC and DC groups received subcutaneous (sc.) injection with a saline solution, while DAT and DET groups received anakinra (10 mg/kg/day, sc.) or etanercept (10 mg/kg, twice a week, sc.), and DEAT rats received both anakinra and etanercept treatments for 21 days after diabetes has developed. Anakinra and etanercept treatments significantly increased insulin and homeostatic model assessment-β cell function levels and decreased glucose levels compared to the DC group as single (DAT and DET) and combined treatments (DEAT). The thiobarbituric acid reactive substances level was significantly decreased in DAT group. The combine use of etanercept and anakinra can improve insulin and blood glucose in type 2 diabetic rats. The combined treatment of anakinra and etanercept together was more effective than single treatment and might have a potential new treatment strategy and to reduce the mortality and morbidity resulting from diabetes.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Pharmacokinetics of marbofloxacin following intramuscular administration at different doses in sheep

The pharmacokinetics of marbofloxacin (MBX) was determined following the intramuscular administration at the doses of 2, 4, 6, and 10 mg/kg in twenty-four healthy sheep. In parallel design, sheep were randomized to 2, 4, 6, and 10 mg/kg dose groups of six animals per group. High performance liquid chromatography method for determination of MBX in sheep plasma was used. Pharmacokinetic parameters were calculated by a non-compartmental method. The dose-normalized the area under the concentration-versus-time curve (AUC(0-infinity)) and dose-normalized maximum plasma concentration (C-max) in 10 mg/kg dose group were significantly higher than other dose groups. The elimination half-life (t(1/2 lambda z)) of marbofloxacin in 10 mg/kg dose group was significantly longer than other dose groups. MBX exhibited dose-proportional pharmacokinetics and was well tolerated after 2, 4, 6 and 10 mg/kg doses in sheep. The 2, 4, 6, and 10 mg/kg doses of MBX could be administered in the treatment of infections caused by susceptible pathogens in sheep. However, additional studies are needed to identify whether MBX is efficient in sheep of naturally infected with susceptible bacteria

Pharmacokinetics and bioavailability of cefquinome and ceftriaxone in premature calves

The aim of this study was to evaluate the pharmacokinetics and bioavailability of cefquinome (CFQ) and ceftriaxone (CTX) following intravenous (IV) and intramuscular (IM) administrations in premature calves. Using a parallel design, 24 premature calves were randomly divided into the two antibiotic groups. Each of the six animals in the first group received CFQ (2 mg/kg) through IV or IM administration. The second group received CTX (20 mg/kg) via the same administration route. Plasma concentrations of the drugs were analyzed by high-performance liquid chromatography and noncompartmental methods. Mean pharmacokinetic parameters of CFQ and CTX following IV administration were as follows: elimination half-life (t(1/2 lambda z)) 1.85 and 3.31 hr, area under the plasma concentration-time curve (AUC(0-infinity)) 15.74 and 174 hr * mu g/ml, volume of distribution at steady-state 0.37 and 0.45 L/kg, and total body clearance 0.13 and 0.12 L hr(-1) kg(-1), respectively. Mean pharmacokinetic parameters of CFQ and CTX after IM injection were as follows: peak concentration 4.56 and 25.04 mu g/ml, time to reach peak concentration 1 and 1.5 hr, t(1/2 lambda z) 4.74 and 3.62 hr, and AUC(0-infinity) 22.75 and 147 hr * mu g/ml, respectively. The bioavailability of CFQ and CTX after IM injection was 141% and 79%, respectively. IM administration of CFQ (2 mg/kg) and CTX (20 mg/kg) can be recommended at 12-hr interval for treating infections caused by susceptible bacteria, with minimum inhibitory concentration values of <= 0.5 and <= 4 mu g/ml, respectively, in premature calves. However, further research is indicated to assess the pharmacokinetic parameters following multiple doses of the drug in premature calves

Determination of temporal changes in hepatic drug-oxidizing capacity using plasma metabolite/caffeine ratios in non-pregnant and pregnant goats

Caffeine (CF) is a metabolic probe drug used in the determination of the hepatic drug-oxidizing capacity. The aim of this study was to investigate temporal changes in the hepatic drug-oxidizing capacity using plasma metabolite/CF ratios in non-pregnant goats (n = 11) and pregnant goats (n = 23). CF (5 mg/kg, intravenous) was administered in six periods (Period 1–6) with 45 days between two periods. The plasma levels of CF and its metabolites, theophylline (TP), theobromine (TB) and paraxanthine (PX), were determined by HPLC-UV. To evaluate hepatic drug-oxidizing capacity in terms of enzymes that play a role in CF metabolism, the plasma metabolic ratios including TB/CF, PX/CF, TP/CF and TB + PX + TP/CF were determined at 10 h following CF administration. Plasma metabolite/CF ratios were similar between non-pregnant and pregnant goats. However, plasma metabolite/CF ratios in Period 3 (45 days in pregnant goats) were significantly higher than those other periods in both pregnant and non-pregnant goats. The effect of pregnancy may not be observed on drugs that are substrates of enzymes involved in CF metabolism in goats