21 research outputs found

    Disposition kinetics of robenacoxib following intravenous and oral administration in geese (Anser anser domesticus)

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    : Robenacoxib (RX) is a veterinary cyclooxygenase-2 selective inhibitor drug. It has never been tested on birds and is only labelled for use in cats and dogs. The purpose of this study was to assess its pharmacokinetics in geese after single intravenous (IV) and oral (PO) administrations. Four-month healthy female geese (n = 8) were used. Geese were subjected to a two-phase, single-dose (2 mg/kg IV, 4 mg/kg PO), open, longitudinal study design with a four-month washout period between the IV and the PO phases. Blood was collected from the left wing vein to heparinized tubes at 0, 0.085 (for IV only), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 24 h. Plasma RX concentrations were measured using HPLC coupled to an UV detector, and the data were pharmacokinetically analysed using ThothProTM 4.3 software in a non-compartmental approach. Following IV administration, terminal elimination half-life, volume of distribution, and total clearance were 0.35 h, 0.34 L/kg, and 0.68 L/h/kg, respectively. For the PO route, the mean peak plasma concentration was 6.78 Όg/mL at 0.50 h. The t1/2λz was very short and significantly different between the IV and PO administrations (0.35 h IV vs. 0.99 h PO), suggesting the occurrence of a flip-flop phenomenon. The Cl values corrected for the F% were significantly different between IV and PO administrations. It might have been a consequence of the longitudinal study design and the altered physiological and environmental conditions after a 4-month washout period. The absolute oral F% computed with the AUC method surpassed 150%, but after normalizing it to t1/2λz, it was 46%. In conclusion, the administration of RX might not be suitable for geese, due to its short t1/2λz

    Robenacoxib pharmacokinetics in sheep following oral, subcutaneous, and intravenous administration

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    The aim of this study was to evaluate the pharmacokinetics (PK) of robenacoxib (RX), a COX-2 selective non-steroidal anti-inflammatory drug, in sheep after single subcutaneous (SC), oral (PO), and intravenous (IV) administration. Five healthy female sheep underwent a three-phase parallel study design with a washout period of 4 weeks, in which sheep received a 4 mg/kg SC dose in phase 1, a 4 mg/kg PO administration in phase 2, and a 2 mg/kg IV administration in phase 3. Plasma RX concentrations were measured over a 48 h period for each treatment using HPLC coupled to a UV multiple wavelength detector, and the PK parameters were estimated using a non-compartmental method. Following IV administration, terminal elimination half-life, volume of distribution at steady state, and total clearance were 2.64 h, 0.077 L/kg, and 0.056 L/h kg, respectively. The mean peak plasma concentrations following SC and PO administrations were 7.04 and 3.01 mu g/mL, respectively. The mean bioavailability following SC and PO administrations were 45.98% and 16.58%, respectively. The SC route may be proposed for use in sheep. However, the multi-dose and pharmacodynamic studies are necessary to establish more accurately its safety and efficacy in sheep

    Metronidazole pharmacokinetics in geese (Anser anser domesticus) after intravenous and oral administrations

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    Metronidazole (MTZ) is a 5-nitroimidazole anti-bacterial and anti-protozoal drug. In human and companion animal medicine, MTZ remains widely used due to its effectiveness against anaerobic bacteria and protozoa. In farm animals, however, MTZ is currently prohibited in several countries due to insufficient data on nitroimidazoles. The purpose of this study was to assess its pharmacokinetics (PK) in geese after single intravenous (IV) and oral (PO) administrations. Fifteen-month old healthy male geese (n = 8) were used. Geese were subjected to a two-phase, single-dose (10 mg/kg IV, 50 mg/kg PO), open, longitudinal study design with a two-week washout period between the IV and PO phases. Blood was drawn from the left wing vein to heparinized tubes at 0, 0.085 (for IV only), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 24, and 48 h. Plasma MTZ concentrations were measured using HPLC coupled to an UV detector, and the data were pharmacokinetically analyzed using PKanalix (TM) software with a non-compartmental approach. MTZ was still quantifiable and well above the LLOQ at 24 h after both routes of administration. Following IV administration, terminal elimination half-life, volume of distribution, and total clearance were 5.47 h, 767 mL/kg, and 96 mL/h/kg, respectively. For the PO route, the bioavailability was high (85%), and the mean peak plasma concentration was 60.27 mu g/mL at 1 h. When parameters were normalized for the dose, there were no statistically significant differences for any of the PK parameters between the two routes of administration. The study shows that oral administration of MTZ seems to be promising in geese, although comprehensive research on its pharmacodynamics and multiple-dose studies are necessary before its adoption in geese can be further considered

    Intoxication of dogs and cats with common stimulating, hallucinogenic and dissociative recreational drugs

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    Pets can have accidental, intentional, or malicious exposure to illicit drugs. It is a growing concern over the last decade because there is an increase in usage of illicit drugs in humans and diagnosis is difficult. Owners are often not aware of exposure, or they are reluctant to admit possession of recreational drugs in the household due to potential legal consequences. In addition, illicit drugs sold on the black market are often adulterated with other substances resulting in non-specific clinical presentation and aggravation of symptoms. There are affordable onsite diagnostic tests on the market which could facilitate diagnosis of intoxication with illicit drugs, but they give a lot of false positive results due to low specificity of the tests. In this paper we gathered information about the most common recreational drugs such as amphetamines, methamphetamine, 3,4-methylenedioxy-methamphetamine (MDMA), phencyclidine (PCP), lysergic acid diethylamide (LSD), psilocybin mushrooms and cocaine in terms of toxicokinetic properties, mechanism of toxic action, clinical presentation and treatment in dogs and cats

    Pharmacokinetics and antibacterial activity of tiamulin after single and multiple oral administrations in geese

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    Tiamulin is an antibiotic approved exclusively in veterinary medicine, active against G-positive bacteria as well as Mycoplasma spp. and Leptospirae spp. The study was aimed to establish its pharmacokinetics and to evaluate drug effects on resistance in cloacal flora in vivo in geese. Eight healthy geese underwent to a two-phase longitudinal study (60 mg/kg single oral administration vs 60 mg/kg/day for 4 days) with a two-week wash-out period. Blood samples and cloacal swabs were collected at pre-assigned times. Minimal inhibitory concentration (MIC) has been evaluated for each isolated bacterial species. The pharmacokinetic parameters that significantly differed between the groups were Cmax (p = 0.024), AUC0-t (p = 0.031), AUC0-inf (p = 0.038), t1/2kel (p = 0.021), Cl/F (p = 0.036), and Vd/F (p = 0.012). Tiamulin exhibited a slow to moderate terminal half-life (3.13 h single; 2.62 h multiple) and a rapid absorption (1 h single; 0.5 h multiple) in geese, with an accumulation ratio of 1.8 after multiple doses. An in-silico simulation of multiple dosing did not reflect the results of the in vivo multiple dosage study. In both treatments, the MIC values were very high demonstrating a resistance (> 64 ÎŒg/ml) against tiamulin that can be present prior the drug administration for some strains, or emerge shortly after the commencing of treatment for some others

    Synopsis of the pharmacokinetics, pharmacodynamics, applications, and safety of firocoxib in horses

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    According to in vitro and in vivo investigations, firocoxib (FX), a second-generation coxib, is a highly selective COX-2 inhibitor in horses. With a COX-1/COX-2 IC50 ratio of 643 in horses, FX spares the COX-1 inhibitory effects. It is approved for the treatment of musculoskeletal problems and lameness in horses and dogs with osteoarthritis (OA). For the treatment of OA in horses, both an injectable formulation for IV administration at a dose of 0.09 mg/kg for five days and an oral paste formulation at a dose of 0.1 mg/kg for 14 days are licensed. Numerous analytical methods were reported in the literature to quantify FX in biological fluids, using HPLC and LC-MS. FX presents remarkable pharmacokinetics and pharmacodynamics compared to other coxibs. It has an oral bioavailability of 80% or higher and is effectively absorbed by horses. Its volume of distribution is around 2 L/kg, and it is slowly eliminated. Due to the long elimination half-life (around 2 days), which allows a once daily dosing, a single 0.3 mg/kg loading dose has been recommended. This enables the establishment of steady-state drug concentrations within 24 h, making it appropriate for acute treatment as well. Its IC80 is equal to 103 ng/mL in whole blood and, with an EC50 of 27 ng/mL, it has the highest affinity for its receptor compared to the other commonly administered NSAIDs in horses
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