Enrofloxacin hydrochloride

Introduction:Enrofloxacin is used in the treatment of a wide variety of bacterial infections in mammals. However, its poor solubility limits the clinical use.Methods:In order to improve the solubility of enrofloxacin, the enrofloxacin mesylate (EM) were obtained by a chemical synthesis method. The characterization of EM was carried out using ultraviolet scan (UV), synchronous thermal analysis (SDT), fourier transform infrared spectrometer (FTIR) and mass spectrometry (MS), nuclear magnetic resonance (NMR) and X-ray powder diffraction analysis (XRPD). Acute toxicity of EM in Kunming mice was studied. Besides, pharmacokinetic studies were performed in New Zealand rabbits at a single oral dose of 10 mg/kg, and the antibacterial activity of EM was also evaluated.Results:EM was successfully synthesized and purified. The stoichiometric ratio of mesylate to enrofloxacin was 1:1 and the aqueous solubility of EM was 483.01±4.06 mg/mL, the solubility of EM was about 2000 times higher than enrofloxacin. The oral lethal dose (LD50) of EM was 1168.364 mg/kg, and the pharmacokinetics indicated that the oral relative bioavailability of EM was about 1.79 times and 1.48 times higher than that of enrofloxacin and enrofloxacin hydrochloride, respectively. In addition, the in vitro antibacterial activity of EM was not significantly changed compared with enrofloxacin and enrofloxacin hydrochloride.Conclusion:EM has higher solubility, low toxicity for oral use, and increases the oral bioavailability in rabbit. This study may be of benefit for the development of new enrofloxacin drugs.

Pharmacokinetic parameters and efficacy prediction indexes (Cmax/MIC90and AUC0-24/MIC90) of an enrofloxacin hydrochloride (ENR-HCl) veterinary product soluble in water were determined in healthy broiler chickens of both sexes after a single oral dose of ENR-HCl (equivalent to 10 mg ENR base/kg bw). Monte Carlo simulations targeting Cmax/MIC90= 10 and AUC0-24/MIC90=125 were also performed based on a set of MIC (minimum inhibitory concentration) values of bacterial strains that induce common clinical diseases in broiler chickens and that showed to be susceptible to ENR-HCl. Plasma concentrations of ENR and its main metabolite ciprofloxacin (CIP) were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Plasma concentration-time curves were found to fit a non-compartmental open model. The ratio of the area under the plasma concentration-time curve (AUC) of CIP/ENR was 4.91%. Maximum plasma concentrations of 1.35 ± 0.15 μg/mL for ENR-HCl and 0.09 ± 0.01 μg/mL for CIP were reached at 4.00 ± 0.00 h and 3.44 ± 1.01 h, respectively. Areas under the plasma vs. time concentration curve in 24 h (AUC0-24) were 18.91 ± 1.91 h × μg/mL and 1.19 ± 0.12 h × μg/mL for ENR-HCl and CIP, respectively. Using a microbroth dilution method, the minimum inhibitory concentration (MIC90) values were determined for ENR-HCl for 10 bacterial strains (Mycoplasma gallisepticum, Mycoplasma synoviae, Avibacterium paragallinarum, Clostridium perfringens, Escherichia coli, Pseudomonas aeruginosa, Salmonellaser. Enteritidis, Salmonellaser. Gallinarum, Salmonellaser. Pullorum, andSalmonellaser. Typhimurium), which are the most common causes of infectious clinical diseases in broiler chickens. In summary, the PK/PD ratios and Monte Carlo simulation were carried out for ENR-HCl in poultry, which due to its solubility was administered in drinking water. The PK/PD efficacy prediction indexes and Monte Carlo simulations indicated that the ENR-HCl oral dose used in this study is useful for bacterial infections in treatingC. perfringens(Gram-positive),E. coliandS. ser. Enteritidis (Gram-negative) andM. gallisepticumbacteria responsible for systemic infections in poultry, predicting a success rate of 100% when MIC ≤ 0.06 μg/mL forE. coliandS. ser. Enteritidis and MIC ≤ 0.1 μg/mL forM. gallisepticum. ForC. perfringens, the success rate was 98.26% for MIC ≤ 0.12. However, clinical trials are needed to confirm this recommendation.

Pharmacokinetics of enrofloxacin HCl-2H2O (enro-C) in dogs and Monte-Carlo simulations againstLeptospiraspp. prompted a clinical study to treat the clinically apparent phase of this disease. Leptospirosis was diagnosed by real-time PCR from blood, micro-agglutination titers (MAT), clinical signs and blood parameters of the liver and kidney. In order to determine the clinical ability of the participants to diagnose leptospirosis on the first exam and establish an early treatment to avoid excessive organ damage, patients were clinically classified as: high-risk or medium-risk. Forty-five dogs were included in this trial (from 2017 to early 2019). The treatment consisted of IM injections of a 5% aqueous enro-C suspension (10 mg/kg/day) for 10 days, and subsequently enro-C was administered orally for another 7 days in gelatin capsules. Thirty-four high-risk and 11 medium-risk dogs were treated, including 6 puppies (4 high-risk with ages between 6 to 10 months and 2 medium-risk dogs with an average age of 6 and 7 months). Other ages ranged from 1 to 5 years. Fifteen cases had a history of having received prior treatment with other antibiotics, including all puppies. The clinical diagnostic error was 13.5% (7/52 cases), and only one of the misdiagnosed dogs had been classified as a high-risk patient. Three to 5 days after finishing treatment with enro-C, 82.2% of the dogs were negative to real-time PCR from urine samples and 100% negativity was observed on day 30 after treatment, when antibody titrations dropped to 1:100-1:200. Based on the absence of clinical signs, real-time PCR, and MAT titers, all treated dogs were considered as successful treatments. Within 6-24 months of clinical follow-up, no relapses were recorded. Adverse effects were inconsequential. This study represents the first report of a successful treatment of canine leptospirosis using a fluoroquinolone, and due to its efficacy, it is suggested that enro-C be considered as a viable option for the treatment of this disease.