Plasma and Red Blood Cells Concentration Profiles of Ktamine after Single Intravenous Administration in an Anaesthetic Protocol in Horses

The aim of this study was to describe the concentration profile of ketamine in plasma and red blood cells following an intravenous (IV) bolus in the horse. Ten healthy standardbred horses (two males and height females) 7.7 ± 4.6 (mean value ± SD) years old and weighting 380 ± 21 kg (mean value ± SD) were recruited. The horses were premedicated with acepromazine (0.04 mg·kg-1·IV). Fifteen minutes later they received romifidine (0.08 mg·kg-1·IV), and 5 minutes after they were administered midazolam (0.06 mg·kg-1·IV). Immediately, anaesthesia was induced by ketamine (2.2 mg·kg-1·IV). Venous blood samples were collected at scheduled time points. Plasma and red blood cells (RBCs) concentration of ketamine was assayed using a high performance liquid chromatographic method (HPLC/UV-DAD). The high mean recovery rates, the high sensitivity, the good linearity, suggest a clinical applicability of the analytical method. A bicompartmental model resulted as the most appropriate to describe the ketamine concentration—time profile for both plasma and RBCs. The fitted regression line between ketamine plasma concentrations and RBC concentrations supports the good correlation between ketamine concentrations in plasma and in RBCs. The kinetic parameters of ketamine calculated for RBC are equal or very similar to the plasma ones. The study confirms the kinetic behaviour of ketamine used in the horse as anaesthetic inducers in routine surgery. Finally, the bicompartmental model well describes the ketamine profile also in RBCs, that it is very close to the plasma profile, underlining the great importance of RBCs as blood subcompartment

Rapid Depletion of Marbofloxacin Residues in Rabbit after Therapeutic Treatment

Although rabbit meat production represents a very small percentage of the world meat market, this percentage has been growing continuously during the last 30 years. Rabbit is considered a minor food species, and therefore no drugs are specifically registered for this animal. This situation encourages rabbit farmers to make off-label use of antibacterial drugs authorized for food-producing animal species other than rabbits. In the present study, the distribution and elimination of the fluoroquinolone antibacterial agent marbofloxacin in rabbit muscle, liver, and kidney was investigated. Marbofloxacin was chosen as a representative of a new generation of antibacterial drugs active against most gram-positive and gram-negative bacteria and mycoplasms; it is well tolerated and has short elimination times in bovine and swine species. Rabbits were treated with marbofloxacin at 2 mg kg of body weight(-1) for 5 days. Residual concentrations in liver, kidney, and muscle tissues were determined posttreatment with high-performance liquid chromatography and fluorescence detection. Marbofloxacin was rapidly distributed and eliminated from rabbit tissues. Concentrations were higher in the liver and kidney than in muscle. However, 48 h after the end of treatment, marbofloxacin concentrations dropped below the maximum residue level fixed for this antibacterial drug in cattle and pigs. Considering the efficacy of marbofloxacin for the treatment of the most common rabbit diseases, its tolerability, and its short elimination time as verified in the present study, use of this antibacterial drug could be extended to therapeutic treatment of rabbits

Pharmacokinetic profile and partitioning in red blood cells of romifidine after single intravenous administration in the horse

The aims of this study were to assess the plasma concentrations of romifidine in horses after intravenous injection, to evaluate the red blood cell (RBC) partitioning of the anaesthetic drug, and to improve knowledge regarding its sedative effect in horses describing the pharmacokinetic model. Eight adult Standardbred horses received a single bolus of romifidine at a dosage of 100\ua0\u3bcg/kg. Blood samples (5\ua0mL) were collected immediately before romifidine administration (t0), and at 2, 5, 10, 15, 20, 25, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180\ua0min after injection. A sedation score was recorded at the same time. The romifidine concentrations in plasma and red blood cells were determined by high performance liquid chromatography (HPLC). The plasma and red blood cell concentrations were correlated with the sedation at each time point. Romifidine produced a satisfactory level of sedation in all animals. The sedation was detectable in all horses for up to 105\ua0min. All the animals returned to normal without any behavioural changes at 180\ua0min. The romifidine concentrations in the red blood cells were significantly higher (P\ua0<\ua00.01) at all time points than those in the plasma. The T1/2\u3b2 was 148.67\ua0\ub1\ua061.59\ua0min and body clearance was 22.55\ua0\ub1\ua06.67\ua0mL/kg per min. The results showed that after a single bolus administration of romifidine, a partitioning in the RBCs was detected

Efficacy of Systemically Administered Retargeted Oncolytic Herpes Simplex Viruses—Clearance and Biodistribution in Naïve and HSV-Preimmune Mice

We investigated the anticancer efficacy, blood clearance, and tissue biodistribution of systemically administered retargeted oncolytic herpes simplex viruses (ReHVs) in HSV-naive and HSV-preimmunized (HSV-IMM) mice. Efficacy was tested against lung tumors formed upon intravenous administration of cancer cells, a model of metastatic disease, and against subcutaneous distant tumors. In naive mice, HER2- and hPSMA-retargeted viruses, both armed with mIL-12, were highly effective, even when administered to mice with well-developed tumors. Efficacy was higher for combination regimens with immune checkpoint inhibitors. A significant amount of infectious virus persisted in the blood for at least 1 h. Viral genomes, or fragments thereof, persisted in the blood and tissues for days. Remarkably, the only sites of viral replication were the lungs of tumor-positive mice and the subcutaneous tumors. No replication was detected in other tissues, strengthening the evidence of the high cancer specificity of ReHVs, a property that renders ReHVs suitable for systemic administration. In HSV-IMM mice, ReHVs administered at late times failed to exert anticancer efficacy, and the circulating virus was rapidly inactivated. Serum stability and in vivo whole blood stability assays highlighted neutralizing antibodies as the main factor in virus inactivation. Efforts to deplete mice of the neutralizing antibodies are ongoing