Diclofenac was responsible for the decimation of Gyps vulture species on the Indian subcontinent during the 1980s and 1990s. Gyps vultures are extremely sensitive (the lethal dose 50 [LD50] ~ 0.1 mg/kg – 0.2 mg/kg), with toxicity appearing to be linked to metabolic deficiency, demonstrated by the long T1/2 (~12 h – 17 h). This is in striking comparison to the domestic chicken (Gallus gallus domesticus), in which the LD50 is ~10 mg/kg and the T1/2 is ~1 h. The phase 1 cytochrome P450 (CYP) 2C subfamily has been cited as a possible reason for metabolic deficiency. The aim of this study was to determine if CYP2C9 homolog pharmacogenomic differences amongst avian species is driving diclofenac toxicity in Gyps vultures. We exposed each of 10 CYP-inhibited test group chickens to a unique dose of diclofenac (as per the Organisation for Economic Co-operation and Development [OECD] toxicity testing guidelines) and compared the toxicity and pharmacokinetic results to control group birds that received no CYP inhibitor. Although no differences were noted in the LD50 values for each group (11.92 mg/kg in the CYP-inhibited test group and 11.58 mg/kg in the control group), the pharmacokinetic profile of the test group was suggestive of partial inhibition of CYP metabolism. Evaluation of the metabolite peaks produced also suggested partial metabolic inhibition in test group birds, as they produced lower amounts of metabolites for one of the three peaks demonstrated and had higher diclofenac exposure. This pilot study supports the hypothesis that CYP metabolism is varied amongst bird species and may explain the higher resilience to diclofenac in the chicken versus vultures.

The pharmacokinetic aspects of tulathromycin (2.5 mg/kg b.w.) were studied following intravenous administration alone and in combination with flunixin meglumine (2.2 mg/kg b.w) in apparently healthy goats. Tulathromycin concentrations in serum were determined by microbiological assay technique using Bacillus subtiles (ATCC 66343) as test organism. The half-lives of distribution and elimination (t0.5(a)and to.5(p)) were 0.071, 0.046 and 6.43, and 5.05 h. following intravenous injection of tulathromycin alone and in combination with flunixin, respectively. Volume of distribution at steady state (Vdss) was 0.249 and 0.96l/kg., mean residence time (MRT) was 6.27 and 5.99 h and total body clearance (ClB) was 0.046 and 0.17 l/kg/hr., respectively. It was concluded that flunixin significantly altered the pharmacokinetics of tulathromycin by increase its distribution and accelerate its elimination from body. Therefore care should be taken during use of tulathromycin in goats concurrently with flunixin.

The pharmacokinetic profile of difloxacin was investigated in camels after single intravenous and intramuscular administration of 5 mg kg-1 b.wt. After i. v. injection, serum concentration time curve was best described as two compartment open model. The distribution and elimination half lives (t0.5 (') and t0.5())) were 0.513± 0.01 h and 6.3±0.15 h. respectively. Difloxacin was distributed extravascularly with a volume of distribution (Vdss) 1.10 ± 0.035 l kg-1., and total body clearance (CLB) of 0.141+ 0.031 l kg-1 h-1. following intramusclar injection, peak serum concentration (Cmax) 2.59 ± 0.19 ug ml-1 attained after Tmax 3.05 ± 0.035 h. The absorption and elimination half lives (t0.5 (ab) and t0.5 (el)) were 0.95 ± 0.003 and 5.86 ± 0.33 h., respectively. The systemic bioavailablility (F) and the plasma protein binding were 87.95 and 23 %, respectively.

Objective: We performed a randomized two-way crossover study to evaluate the pharmacokinetic profiles of two high-dose ascorbic acid (AA) after IV infusion in healthy beagle dogs. Materials and Methods: The dogs were administered IV AA at two doses of 1.5 and 3 gm/kg for 4 h, and the AA concentration in plasma and urine pH was measured before and after administration. Results: The plasma concentrations of AA in both groups peaked 3 h after administration. Among the two groups, the urine pH was not significantly different (p = 0.12990.7944). High-dose IV AA did not induce serious adverse events in dogs. Conclusion: The results of this study suggest that the high dose of AA which reaches the therapeutic dose for cancer and supports the safety of high-dose IV AA in dogs. [J Adv Vet Anim Res 2019; 6(4.000): 481-485]

Objective: The object of the study was to examine the major pharmacokinetic parameters after a single application of a complex drug preparation for veterinary use based on fipronil, praziquantel, moxidectin, and pyriproxyfen in cats and dogs.Materials and Methods: For dogs, the drug preparation was administered spot-on solution in the following dosage of active pharmaceutical substances: fipronil 27.0 mg/kg body weight (bwt), praziquantel 10.8 mg/kg bwt, moxidectin 6.75 mg/kg bwt, and pyriproxyfen 5.4 mg/kg bwt; for cats, the dosage was the following: fipronil 43.2 mg/kg bwt, praziquantel 17.28 mg/kg bwt, mox-idectin 4.32 mg/kg bwt, and pyriproxyfen 8.64 mg/kg bwt. The blood samples were taken from dogs and cats. The principle of the method for determining praziquantel, trans-4-hydroxyprazi-quantel, pyriproxyfen, and fipronil in serum samples was chromatographed in a high-pressure liquid chromatograph with detection by means of a mass-spectrometric detector. The moxidectin content of the blood was detected by high-performance liquid chromatography.Results: The drug preparation active substances: praziquantel, fipronil, and moxidectin are absorbed into the blood of dogs and cats. The penetration of praziquantel into the systemic circulation and further into organs and tissues was proved. After topical administration, moxidectin is absorbed and distributed systemically and is slowly removed from the plasma, which manifests itself in detectable concentrations of moxidectin in the blood for 1 month.Conclusion: The present results of pharmacokinetic investigations may promote to the determination of effective therapy strategy and prophylaxis of parasitic diseases in dogs and cats. [J Adv Vet Anim Res 2019; 6(1.000): 25-32]