Enrofloxacin pharmacokinetics in yellow catfish (Pelteobagrus fulvidraco): A comparative analysis of oral, intramuscular, and bath administration.

Enrofloxacin (ENR) residues in yellow catfish (Pelteobagrus fulvidraco) often exceed the standard due to excessive use. This study explored the pharmacokinetics of ENR and its metabolite ciprofloxacin (CIP) in yellow catfish following a single dose of 10 mg/kg body weight via intramuscular injection (IM), oral gavage (PO), or a 5-h drug bath at 10 mg/L and 25°C. High-performance liquid chromatography-mass spectrometry was used to determine the ENR and CIP concentrations in various tissues. The highest ENR concentration occurred with IM administration, peaking at 4.124 mg/L in the plasma, 8.359 mg/kg in the kidney, 6.272 mg/kg in the liver, and 5.192 mg/kg in the muscle. However, PO administration resulted in the longest metabolic time, with elimination half-lives of 56.47 h in plasma, 86.43 h in the kidney, 76.25 h in the liver, and 64.75 h in muscle. Additionally, the area under the concentration-time curve values for IM, PO, and bath administration in yellow catfish plasma were 108.36, 88.96, and 22.08 mg·h/L, respectively. These results indicate the effectiveness of all three administration methods in treating bacterial diseases in yellow catfish. The selection of an appropriate administration method depends on the minimal inhibitory concentration of ENR against pathogenic bacteria. Yellow catfish subjected to PO and IM administration require longer resting periods before they can be marketed than those receiving drug bath administration.

Pharmacokinetics, withdrawal period and risk assessment of enrofloxacin in the northern snakehead (Channa argus) following bath administration.

Enrofloxacin (ENR) is widely used in aquaculture practice, but little is known about its pharmacokinetic, withdrawal period and dietary risk in fish via bath administration. The purpose of this study was to provide data support for the use of ENR bath therapy in the northern snakehead (Channa argus). The pilot study was carried out to evaluate the therapy concentrations of ENR in northern snakehead with immersion concentrations ranged from 5 to 40 mg/L for 6 h. Based on results of the pilot study, an ENR immersion concentration of 20 mg/L was used for the formal experiment. At this dose, the peak concentrations of ENR in plasma, muscle plus skin, liver and kidney were 4.85, 4.55, 3.87 and 7.42 µg/mL (or g), respectively. According to the AUC0-∞ values, the distribution of ENR in northern snakehead followed the order of kidney > plasma > liver > muscle + skin. The elimination of ENR in northern snakehead was very slow, the half-lives (T1/2λz ) were up to 90.31, 85.5, 104.56 and 120.9 h in plasma, muscle plus skin, liver and kidney, respectively. Ciprofloxacin (CIP) was not detected in any samples in the pilot study and was only occasionally detected in muscle plus skin and liver samples in formal experiment. Based on the calculated PK/PD index AUC/MIC and Cmax /MIC, the current bath treatment regimen will have a good therapeutic effect on infections caused by bacteria with MIC below 0.6 µg/mL. The dietary risk assessment suggested that there was a dietary risk (Hazard Quotients > 10%) until day 6 after bath treatment. It is mandatory for ENR to maintain a withdrawal period of at least 450°C-day in northern snakehead after bath treatment ceased.

Comparative Pharmacokinetics of Intravenous Enrofloxacin in One- Six- And Twelve-Month-Old Sheep.

BACKGROUND: Enrofloxacin (ENR) is a fluoroquinolone antibiotic approved for use in sheep of all ages. The body composition and metabolic capability change with age. These changes may alter the pharmacokinetics of drugs and thus their effect. Therefore, the pharmacokinetics of drugs need to be established in target- age animals. OBJECTIVE: To determine the pharmacokinetics of ENR and its active metabolite, ciprofloxacin (CIP), following a single intravenous administration of ENR at a dose of 10 mg/kg in different ages of sheep. METHODS: The study was carried out in the one-, six- and twelve-month age period of the sheep. A single dose of 10 mg/kg ENR was administered intravenously through the jugular vein to sheep in all age periods. ENR and CIP plasma concentrations were determined using HPLC-UV and analyzed using a non-compartmental method. RESULTS: ENR was detected in the plasma until 36 h in one-month-old and up to 24 h in other ages. CIP was detected in the plasma up to 24 h in all age groups. The t1/2ʎz and Vdss were significantly higher in one-month-old sheep than in six and twelve-months old sheep. There was no difference in ClT and AUC values in different age groups. AUC0-∞CIP/AUC0-∞ENR ratios were higher in one-month-old than in six- and twelve-months sheep. CONCLUSION: The most important pharmacokinetic changes associated with aging in sheep are decreased Vdss and t1/2ʎz of ENR and the low ratio metabolizing of ENR to CIP. Pharmacokinetic/pharmacodynamic data showed that ENR after IV administration of 10 mg/kg dose provided the optimal AUC0-24/MIC90 ratios for E. coli, P. multocida and Mycoplasma spp. (>125) with MIC of 0.37 µg/mL and for S. aureus (>30) with MIC of 0.5 µg/mL in all ages of sheep.

Pharmacokinetics, withdrawal time, and dietary risk assessment of enrofloxacin and its metabolite ciprofloxacin, and sulfachloropyridazine-trimethoprim in Taihe black-boned silky fowls.

Enrofloxacin (ENR) and sulfachloropyridazine combined with trimethoprim (TMP) were commonly used in poultries to treat bacterial infections. In this study, the pharmacokinetics of these antibiotics in four tissues of Taihe black-boned silky fowls was studied. The results showed that these drugs were absorbed and distributed rapidly, with the highest concentration showing in skin. Meanwhile, ENR and its metabolite ciprofloxacin (CIP) and TMP were depleted slowly, particularly in skin with the elimination half-lives being 37.1, 36.9, and 72.7 days, respectively. It may be attributed to the abundance of melanin in skin. The dietary risk assessment suggested that the long-term dietary intakes of ENR, CIP, and TMP showed a considerable threat to human health. Based on the experiment, the withdrawal times of 284 days for ENR + CIP and 159 days for TMP were acquired, which showed that these drugs are not appropriate for the application in Taihe black-boned silky fowls.

Pharmacokinetics and pharmacodynamics of enrofloxacin treatment of Escherichia coli in a murine thigh infection modeling.

BACKGROUND: Enrofloxacin is an antibacterial drug with broad-spectrum activity that is widely indicated for veterinary use. We aim to develop the clinical applications of Enrofloxacin against colibacillosis by using the neutropenic mice thigh infection model. RESULTS: The minimum inhibitory concentration (MIC) distribution of 67 isolated E. coli strains to ENR was calculated using CLSI guidelines. Whereas, the MIC50 value calculation was considered as the population PD parameter for ENR against E. coli strains. The MIC values of 15 E. coli strains were found to be nearest to the MIC50 i.e., 0.25 µg/mL. Of all the tested strains, the PK-PD and E. coli disease model was established via selected E. coli strain i.e., Heilong 15. We analyzed the PK characteristics of ENR and its metabolite ciprofloxacin (CIP) following a single subcutaneous (s.c.) injection of ENR (1.25, 2.5, 5, 10 mg/kg). The concentration-time profiling of ENR within the plasma specimens was determined by considering the non-compartmental analysis (NCA). The basic PK parameters of ENR for the peak drug concentration (Cmax) and the area under the concentration-time curve (AUC) values were found to be in the range of 0.27-1.97 µg/mL and 0.62-3.14 µg.h/mL, respectively. Multiple s.c. injection over 24 h (1.25, 2.5, 5, 10 mg/kg at various time points i.e., 6, 8, 12, and 24 h respectively) were administered to assess the targeted PD values. The Akaike Information Criterion (AIC) was used to choose PD models, and the model with the lowest AIC was chosen. The inhibitory Emax model was employed to calculate the related PK-PD parameters. The results of our study indicated that there was a strong correlation between the AUC/MIC and various antibacterial activities (R2 = 0.9928). The target values of dividing AUC/MIC by 24 h for bacteriostatic action were 1-log10 reduction, 2-log10 reduction, and 3-log10 reduction 0.325, 0.4375, 0.63, and 0.95 accordingly. CONCLUSION: The identified pharmacodynamics targets for various antibacterial effects will be crucial in enhancing ENR clinical applications and serving as a key step in reducing bacterial resistance.

Structural characterization and pharmacological assessment in vitro/in vivo of a new copper(II)-based derivative of enrofloxacin.

Enrofloxacin (EFX) was selected as the medicinal ligand to afford a new copper(ii)-based complex, EFX-Cu, which was structurally characterized by spectroscopic analyses including X-ray single crystal diffraction. It was also stable and could retain the coordination state in aqueous solution. The in vitro antibacterial activity of EFX-Cu against a panel of pathogenic bacteria was about the same as that of EFX, except that it was twice as active against E. coli. The in vivo test on mice gave a LD50 value of 8148 mg kg-1 for EFX-Cu, which was much lower than those for EFX (LD50, 5312 mg kg-1) and its clinically used sodium salt, EFX-Na (LD50, 1421 mg kg-1). In addition, no obvious lesions in the organs of the dead mice were found by histopathological examination. Pharmacokinetic studies on rats suggested similar pharmacokinetics between EFX-Cu and EFX. On the other hand, EFX-Cu showed higher acute toxicity than EFX-Na in zebrafish, which was inconsistent with that in mice. The ROS-related inflammation and anti-inflammatory assay of EFX-Cu, respectively, in normal cells and zebrafish could be ascribed to its ROS-related redox property. Unfortunately, the final in vivo therapeutic assay in the E. coli-infected mouse model indicated that the therapeutic effect of EFX-Cu, mainly in terms of mortality in mice, was found to be lower than that of EFX-Na at the same dosage (800 mg kg-1, continuous gavage), although the contradictory factors between toxicity and antibacterial activity could not be excluded in this trial.

The impact of therapeutic-dose induced intestinal enrofloxacin concentrations in healthy pigs on fecal Escherichia coli populations.

BACKGROUND: Knowledge of therapy-induced intestinal tract concentrations of antimicrobials allows for interpretation and prediction of antimicrobial resistance selection within the intestinal microbiota. This study describes the impact of three different doses of enrofloxacin (ENR) and two different administration routes on the intestinal concentration of ENR and on the fecal Escherichia coli populations in pigs. Enrofloxacin was administered on three consecutive days to four different treatment groups. The groups either received an oral bolus administration of ENR (conventional or half dose) or an intramuscular administration (conventional or double dose). RESULTS: Quantitative analysis of fecal samples showed high ENR concentrations in all groups, ranging from 5.114 ± 1.272 µg/g up to 39.54 ± 10.43 µg/g at the end of the treatment period. In addition, analysis of the luminal intestinal content revealed an increase of ENR concentration from the proximal to the distal intestinal tract segments, with no significant effect of administration route. Fecal samples were also screened for resistance in E. coli isolates against ENR. Wild-type (MIC≤0.125 µg/mL) and non-wild-type (0.125 < MIC≤2 µg/mL) E. coli isolates were found at time 0 h. At the end of treatment (3 days) only non-wild-type isolates (MIC≥32 µg/mL) were found. CONCLUSIONS: In conclusion, the observed intestinal ENR concentrations in all groups showed to be both theoretically (based on pharmacokinetic and pharmacodynamic principles) and effectively (in vivo measurement) capable of significantly reducing the intestinal E. coli wild-type population.

Pharmacokinetics in plasma and alveolar regions of healthy calves subcutaneously administered a single dose of enrofloxacin.

This study aimed to analyze the pharmacokinetics of enrofloxacin (ERFX) and its metabolite ciprofloxacin (CPFX) in plasma, as well as their migration to, and retention in, the epithelial lining fluid (ELF) and alveolar cells within the bronchoalveolar fluid (BALF). Four healthy calves were subcutaneously administered a single dose of ERFX (5 mg/kg). ERFX and CPFX dynamics post-administration were analyzed via a non-compartment model, including the absorption phase. The Cmax of plasma ERFX was 1.6 ± 0.4 µg/ml at 2.3 ± 0.5 hr post-administration and gradually decreased to 0.14 ± 0.03 µg/ml at 24 hr following administration. The mean residence time between 0 and 24 hr (MRT0-24) in plasma was 6.9 ± 1.0 hr. ERFX concentrations in ELF and alveolar cells peaked at 3.0 ± 2.0 hr and 4.0 ± 2.3 hr following administration, respectively, and gradually decreased to 0.9 ± 0.8 µg/ml and 0.8 ± 0.5 µg/ml thereafter. The plasma half-life (t1/2) of ERFX was 6.5 ± 0.7 hr, while that in ELF and alveolar cells was 6.5 ± 3.6 and 7.4 ± 4.3 hr, respectively. The Cmax and the area under the concentration-time curve for 0-24 hr for ERFX were significantly higher in alveolar cells than in plasma (P<0.05). These results suggest that ERFX is distributed at high concentrations in ELF and is retained at high concentrations in alveolar cells after 24 hr in the BALF region; hence, ERFX may be an effective therapeutic agent against pneumonia.

Synthesis, Characterization, and Pharmacodynamics Study of Enrofloxacin Mesylate.

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.

Formation of inclusion complex of enrofloxacin with 2-hydroxypropyl-ß-cyclodextrin.

Enrofloxacin, a third-generation fluoroquinolone, is a broad-spectrum antimicrobial drug against a lot of veterinary bacterial diseases. However, bactericidal activity of enrofloxacin is concentration-dependent and its poor aqueous solubility and bitter taste limit its development and application. Meanwhile, 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD), a widely used cyclodextrin analog, is a safe and an effective drug carrier. It forms inclusion complexes with its drug substrates and improves their physiochemical and pharmacokinetic properties. Enrofloxacin was also found to form a stable inclusion complex with HP-ß-CD and different research groups have shown improved solubility for enrofloxacin by 32.5%, 9.25 and 165-fold. Our own efforts in this direction resulted in manifold improvement (916-fold) in its solubility compared to the previous studies. It was further shown that pharmaceutical properties, absorption and bioavailability, of enrofloxacin have also been significantly improved by complexation with HP-ß-CD.

Population pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in clinically diseased or injured Eastern box turtles (Terrapene carolina carolina), yellow-bellied sliders (Trachemys scripta scripta), and river cooters (Pseudemys concinna).

Enrofloxacin is frequently administered to turtles in wildlife clinics during rehabilitation due to its wide spectrum of antibacterial activity and availability of injectable formulations. However, sufficient pharmacokinetic data to guide dosing are lacking. The objective of this study was to determine pharmacokinetic parameters of enrofloxacin and its active metabolite, ciprofloxacin, in chelonians presenting injured to a wildlife clinic. Thirty-six Eastern box turtles (EBT, Terrapene carolina carolina), 23 yellow-bellied sliders (YBS, Trachemys scripta scripta), and 13 river cooters (RC, Pseudemys concinna) received a single subcutaneous injection of enrofloxacin at 10 mg/kg. Blood samples were collected between 0 and 240 hr postinjection. Pharmacokinetic parameters were determined using nonlinear mixed-effects modeling (NMLE). Overall elimination half-life (T½) was over 75 hr, and varied among species. T½ was 63 hr in EBT and 79 hr in YBS, which is longer than in previous reports. The volume of distribution (steady-state) was 1.4 L/kg across turtle species, but highly variable-ranging from 0.4 L/kg in RC to 1.9 L/kg in YBS. Antibiotic concentrations were above a minimum inhibitory concentration value of 0.5 µg/ml for over 200 hr. These results indicate variable pharmacokinetic parameters for enrofloxacin among turtle species, which will help guide appropriate dosing protocols in injured turtles.

Pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in freshwater crocodiles (Crocodylus siamensis) after intravenous and intramuscular administration.

To the best of the authors' knowledge, pharmacokinetic information to establish suitable therapeutic plans for freshwater crocodiles is limited. Therefore, the purpose of this study was to clarify the pharmacokinetic characteristics of enrofloxacin (ENR) in freshwater crocodiles, Crocodylus siamensis, following single intravenous and intramuscular administration at a dosage of 5 mg/kg body weight (b.w.). Blood samples were collected at assigned times up to 168 hr. The plasma concentrations of ENR and its metabolite ciprofloxacin (CIP) were measured by liquid chromatography tandem-mass spectrometry. The concentrations of ENR and CIP in the plasma were quantified up to 144 hr after both the administrations. The half-life was long (43-44 hr) and similar after both administrations. The absolute i.m. bioavailability was 82.65% and the binding percentage of ENR to plasma protein ranged from 9% to 18% with an average of 10.6%. Percentage of CIP (plasma concentrations) was 15.9% and 19.9% after i.v. and i.m. administration, respectively. Based on the pharmacokinetic data, susceptibility break point and PK-PD indexes, i.m. single administration of ENR at a dosage of 5 mg/kg b.w. might be appropriate for treatment of susceptible bacteria (MIC > 1 µg/mL) in freshwater crocodiles, C. siamensis.

Pharmacokinetics and tissue residues of enrofloxacin in the largemouth bass (Micropterus salmoides) after oral administration.

The study was carried out to evaluate the pharmacokinetic disposition of enrofloxacin (ENF) with a single dose of 20 mg/kg after oral administration in largemouth bass (Micropterus salmoides) at 28°C. The concentrations of ENF and of its metabolite ciprofloxacin (CIP) in plasma, liver, and muscle plus skin in natural proportions were determined using HPLC. The concentration-time data for ENF in plasma were best described by a two-compartment open model. After oral administration, the maximum ENF concentration (Cmax ) of 10.99 µg/ml was obtained at 0.60 hr. The absorption half-life (T1/2Ka ) of ENF was calculated to be 0.07 hr whereas the elimination half-life (T1/2ß ) of the drug was 90.79 hr. The estimates of area under the plasma concentration-time curve (AUC) and apparent volume of distribution (Vd/F) were 1,185.73 µg hr/ml and 2.21 L/kg, respectively. ENF residues were slowly depleted from the liver and muscle plus skin of largemouth bass with the T1/2ß of 124.73 and 115.14 hr, respectively. Very low levels of ciprofloxacin were detected in the plasma and tissues. A withdrawal time of 24 days was necessary to ensure that the residues of ENF + CIP in muscle plus skin were less than the maximal residue limit (MRL) of 100 µg/kg established by the European Union.

The influence of age and body weight gain on enrofloxacin pharmacokinetics in turkeys-Allometric approach to dose optimization.

Enrofloxacin is a concentration-dependent antimicrobial used in bacterial infections in poultry. During a few months of a turkey's life, pharmacokinetics of drugs undergoes substantial changes which may compromise their efficacy due to variability in internal exposure (measured by area under the concentration-time curve, AUC). The aim of this study was to describe the effects of age on the pharmacokinetics of a single intravenous (i.v.) and oral administration of enrofloxacin at a dose of 10 mg/kg to turkeys. It was found that during a 2.5-month-long period of growth from 1.4 to 14.6 kg, the AUC after i.v. administration increased almost threefold due to a significant decrease in the body clearance (from a mean of 0.76-0.28 L hr-1  kg-1 ). Over the same period, the mean elimination half-life was prolonged from 2.65 to 7.03 hr. Oral administration resulted in a similar trend in pharmacokinetic parameters. For both routes, formation of the major metabolite, ciprofloxacin, was marginal. Protein binding was not age-dependent and never exceeded 50%. Body clearance, volume of distribution and elimination half-life were subjected to an allometric analysis and a novel, nonlinear dosage protocol has been proposed to improve the internal exposure to the drug in different age groups of turkeys.

Implications for dosing regimen of enrofloxacin administered concurrently with dexamethasone in febrile buffalo calves.

The objective of the study was to determine the influence of dexamethasone (DXM) on pharmacokinetics (PK) and pharmacodynamics (PD) of enrofloxacin (ENR) for dosage optimization following concurrent administration of ENR and DXM in febrile buffalo calves. A 2 µg/kg intravenous dosage of lipopolysaccharide derived from Escherichia coli was used to induce fever in calves. After inducing fever, ENR was administered at the dose rate of 12 mg/kg, IM followed by IM injection of DXM (0.05 mg/kg) in calves. Minor alterations in PK of ENR were observed following the administration of ENR + DXM. The PK parameters were t1/2K10 = 6.34 h, Cl/F = 0.729 L/kg/h, and MRT0-∞ = 10.5 h. Antibacterial activity (MIC, MBC, ex vivo time-kill kinetics) of ENR for P. multocida was not affected by DXM. But MPC of ENR against P. multocida was lessened in presence of DXM. Using PK-PD-modeled AUC0-24h/MIC values for bactericidal effect against P. multocida, daily dosages of ENR administered in combination with DXM were 4.02 mg/kg and 16.1 mg/kg, respectively, for MIC90s of 0.125 µg/ml and 0.50 µg/ml. A dose of 5.38 mg/kg was determined for ENR for frequently occurring P. multocida infections having ≤ MIC90 of 0.125 µg/ml and PK-PD modeled dose was comparable with the recommended ENR dose of 5 mg/kg for bovines for mild infections. It is suggested that a recommended dosage of 5-12.5 mg/kg of ENR can be used effectively in combination with DXM to treat P. multocida associated infections in buffalo calves without any risk of resistance amplification.

Diffusion of fluoroquinolones into equine fetal fluids did not induce fetal lesions after enrofloxacin treatment in early gestation.

While recent work demonstrated that enrofloxacin and ciprofloxacin reach the fetoplacental unit without causing obvious lesions in the 9-month-old equine fetus or resulting foal, many practitioners still hesitate to prescribe a fluoroquinolone during pregnancy. Since early gestation is a critical time for fetal skeletal development, if fluoroquinolones are chondrotoxic to the fetus at any point during gestation, this period would be important. The aim of this study was to assess the effects of 2 weeks' exposure to enrofloxacin on the equine fetus between 46 and 60 days gestation. Twelve pregnancies from nine healthy mares were allocated into two groups: untreated (n=7), or treatment (7.5mg/kg enrofloxacin, PO×14days, n=6). Abortion was induced with prostaglandin 24h after the last enrofloxacin dose, or on the equivalent day of gestation for untreated mares. Four of nine mares were rebred for a second cycle and were assigned to the opposite treatment to serve as their own controls. Fetal fluids from treated mares were analysed for enrofloxacin and ciprofloxacin concentrations. Fetal organs (heart, lungs, spleen, kidney, and liver) and limbs were examined histopathologically. Enrofloxacin and ciprofloxacin diffused to the fetal fluids during early gestation and did not result in detectable abnormalities in the fetus after 14 days of treatment. While current research does not determine long-term foal outcomes, enrofloxacin may be useful for select bacterial infections in pregnant mares.

Evaluation of allometric scaling as a tool for extrapolation of the enrofloxacin dose in American black vultures (Coragyps atratus).

OBJECTIVE: To determine the pharmacokinetics of enrofloxacin after IV administration in American black vultures (Coragyps atratus), to compare clearance of enrofloxacin in American black vultures with clearance of this fluoroquinolone in other avian species, and to evaluate whether allometric scaling is an appropriate tool for dose extrapolation in avian species. ANIMALS: 6 healthy adult American black vultures. PROCEDURES: Enrofloxacin concentrations were quantified by use of high-performance liquid chromatography. Pharmacokinetics of enrofloxacin was determined in American black vultures after IV administration. Pharmacokinetic parameters for 12 avian species obtained from 24 pharmacokinetic studies were used. Allometric analysis of enrofloxacin pharmacokinetic parameters was performed. RESULTS: Volume of distribution at steady state for enrofloxacin was 3.47 L/kg, clearance was 0.147 L/h·kg, and elimination half-life was 18.3 hours. Comparisons among avian species revealed that American black vultures had the lowest extraction ratio for enrofloxacin (1.04%). Only the volume of distribution at steady state and clearance had a good allometric fit. Goodness of fit was improved when ratites were not included in the analysis. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that the use of allometric scaling for the prediction of volume of distribution at steady state could provide a suitable method for extrapolation of enrofloxacin doses among avian species; however, allometric scaling could not be used to adequately predict the clearance of enrofloxacin.

Pharmacokinetics of enrofloxacin and danofloxacin in premature calves.

The aim of this study was to determine the pharmacokinetics/pharmacodynamics of enrofloxacin (ENR) and danofloxacin (DNX) following intravenous (IV) and intramuscular (IM) administrations in premature calves. The study was performed on twenty-four calves that were determined to be premature by anamnesis and general clinical examination. Premature calves were randomly divided into four groups (six premature calves/group) according to a parallel pharmacokinetic (PK) design as follows: ENR-IV (10 mg/kg, IV), ENR-IM (10 mg/kg, IM), DNX-IV (8 mg/kg, IV), and DNX-IM (8 mg/kg, IM). Plasma samples were collected for the determination of tested drugs by high-pressure liquid chromatography with UV detector and analyzed by noncompartmental methods. Mean PK parameters of ENR and DNX following IV administration were as follows: elimination half-life (t1/2λz ) 11.16 and 17.47 hr, area under the plasma concentration-time curve (AUC0-48 ) 139.75 and 38.90 hr*µg/ml, and volume of distribution at steady-state 1.06 and 4.45 L/kg, respectively. Total body clearance of ENR and DNX was 0.07 and 0.18 L hr-1  kg-1 , respectively. The PK parameters of ENR and DNX following IM injection were t1/2λz 21.10 and 28.41 hr, AUC0-48 164.34 and 48.32 hr*µg/ml, respectively. The bioavailability (F) of ENR and DNX was determined to be 118% and 124%, respectively. The mean AUC0-48CPR /AUC0-48ENR ratio was 0.20 and 0.16 after IV and IM administration, respectively, in premature calves. The results showed that ENR (10 mg/kg) and DNX (8 mg/kg) following IV and IM administration produced sufficient plasma concentration for AUC0-24 /minimum inhibitory concentration (MIC) and maximum concentration (Cmax )/MIC ratios for susceptible bacteria, with the MIC90 of 0.5 and 0.03 µg/ml, respectively. These findings may be helpful in planning the dosage regimen for ENR and DNX, but there is a need for further study in naturally infected premature calves.

Effects of lactic acid on drug-metabolizing enzymes in Chinese mitten crab (Eriocheir sisnensis) after oral enrofloxacin.

Enrofloxacin (ENR) is the most commonly used antibiotic in crustacean farming in China. Diet supplementation with lactic acid (LA) may, however, affect the efficacy and safety of ENR-based drugs. The aims of this study were to investigate the effects of LA on drug residues and elimination of oral ENR in Chinese mitten crab (Eriocheir sinensis) and to determine ENR and gene expression levels of drug-metabolizing enzymes in the hepatopancreas. To this end, ENR was orally administered to the crabs at a dose of 10.0 mg kg-1 body weight on the eighth day after feeding diets supplemented with 0.3%LA. The results showed that ENR levels in the hepatopancreas were significantly different at 1 and 12 h between the ENR and ENR + 0.3% LA groups (P < 0.05). Lactic acid did not significantly affect the expression of CYP2A (phase I). However, the expressions of CYP3 (phase I) and GST (phase II) were significantly up-regulated by LA during the elimination process of ENR (6-24 h). At Tmax (1 h), the expression of phosphoenolpyruvate carboxykinase (PEPCK) was induced and expression of succinate dehydrogenase (SDH) was inhibited by LA. Both of these enzymes were significantly inhibited during the elimination process of ENR. The results suggest that LA contributes to the elimination of ENR, and thus, enhances hepatopancreas biotransformation and anti-injury capacity in E. sinensis.

Investigations of structural, spectral and electronic properties of enrofloxacin and boron complexes via quantum chemical calculation and molecular docking.

Quantum chemical analyses were performed over enrofloxacin and boron complexes. The most stable isomer of enrofloxacin was examined at M062X/6-31+G(d) level in gas phase. Structural and spectral characterizations of enrofloxacin and its complexes were performed at same level of theory. MEP maps of studied compound were calculated via ESP charges analyses. Some quantum chemical descriptors (QCDs) were calculated to determine the non-linear optical (NLO) and biological reactivity of studied molecules. Furthermore, molecular docking calculations between boron complexes and a protein (ID: 2ITN and 2ITV) were done. ADME analyses were done in the determination of the best drug candidate. As a result, complex (3) was found as the best in the NLO applications and it was found that complex (1) and (3) have similar biological reactivity in lung cancer treatment.