Preparation of various solid-lipid beads for drug delivery of enrofloxacin

Solid-lipid beads were prepared to retard the release rate of enrofloxacin and to mask its bitter taste using carrageenan or sodium alginate as a shell material and either cacao butter or Witepsol W-35 as a solid lipid core. Sodium alginate was a better shell material than carrageenan and the highest loading efficiency was obtained using 2% sodium alginate. The alginate beads had a spherical morphology and a sturdy shell structure. The enrofloxacin release rate at room temperature was greatly reduced. Solid-lipid beads have the potential to mask the bitter taste of enrofloxacin and extend its release rate.     

Pharmacokinetic-pharmacodynamic indices of enrofloxacin in Escherichia coli O78/H12 infected chickens

Aim of the study was to evaluate the effect of quercetin and enrofloxacin with/without quercetin on elimination of pathogen Escherichia coli O78/H12 in infected chickens. Effect of quercetin on disposition of enrofloxacin was investigated and Pharmacokinetic-pharmacodynamic indices were calculated.Enrofloxacin was absorbed after oral administration in infected animals but with large inter-individual variations. Low concentrations of its main metabolite, ciprofloxacin, were found which could be explained with marked reduction of enrofloxacin transformation in infected animals. Quercetin significantly decreased bioavailability of enrofloxacin and its transformation to ciprofloxacin. Lower formation of metabolite was also found in the studied tissues as spleen, heart, lungs and in liver of group treated in combination with quercetin. Results in infected and quercetin (50 mg/kg) treated group shows lower percentage of re-isolates of the pathogen bacteria in comparison to infected and untreated animals, and close to the low dose (10 mg/kg) of enrofloxacin. High dose of enrofloxacin given in a short time in an infection model with high inoculum size, resulted in better eradication of bacteria although re-isolates could be found in spleen. Additional improvement of the outcome of fluoroquinolone therapy could be searched in early start of drug administration according to the terms of metaphylaxis.     

Preparation of Various Solid-Lipid Beads for Drug Delivery of Enrofloxacin

Solid-lipid beads were prepared to retard the release rate of enrofloxacin and to mask its bitter taste using carrageenan or sodium alginate as a shell material and either cacao butter or Witepsol W-35 as a solid lipid core. Sodium alginate was a better shell material than carrageenan and the highest loading efficiency was obtained using 2% sodium alginate. The alginate beads had a spherical morphology and a sturdy shell structure. The enrofloxacin release rate at room temperature was greatly reduced. Solid-lipid beads have the potential to mask the bitter taste of enrofloxacin and extend its release rate.     

Retinal safety of a new fluoroquinolone,pradofloxacin, in cats: assessment with electroretinography

Purpose To investigate the safety of a new fluoroquinolone, pradofloxacin, on the cat retina using electroretinogram. Methods Ganzfeld ERGs were recorded in 40 cats treated orally for 23 days in 4 groups: CTRL (n = 9): placebo-vehicle; PRADO30 (n = 10): pradofloxacin 30 mg/kg/day; PRADO50 (n = 14): pradofloxacin 50 mg/kg/day; and ENRO30 (n = 7): enrofloxacin at toxic doses of 30 mg/kg/day. ERG was performed before treatment and once weekly during the treatment period. An extended ISCEV protocol with addition of 8 steps of increasing luminance in dark adapted condition was carried out to assess: V _max (saturated scotopic b-wave amplitude) and k (luminance inducing V _max/2). OCT and retinal histological changes were also investigated. Results Pradofloxacin showed no effects in respect to rod b-wave, V _max, k and maximum scotopic a-wave (P > 0.05). Oscillatory potentials, cone ERG and flicker were also unaltered (P > 0.05). Rod b-wave was undetectable after treatment in ENRO30 group, V _max was reduced to 10.5% of the baseline (P < 0.05), accompanied by an increase of k by 1 log cd s/m2 (P < 0.05). Oscillatory potentials, cone b-wave amplitude and 30 Hz flicker amplitude were reduced to 8.3%, 58.9% and 37.4% of the baseline, respectively (P < 0.05). Effects were also seen in OCT and retinal histology starting within one week after the start of treatment and thereafter remaining stable. Conclusion Pradofloxacin at 6 and 10 times the recommended doses was shown to have no retinal toxic effects in cats, neither on rod or cone function with ERG.     

Preparation and characterization of enrofloxacin/carbopol complex in aqueous solution

Since the bitter taste of enrofloxacin apparently limit the patient compliance in the oral formulations of the antibacterial agent, the masking of the taste is essential for the improvement of the therapeutic effectiveness. Therefore, this study was carried out to examine the feasibility of taste masking of enrofloxacin by the retardation of its dissolution rate using the formation of complex between the drug and Carbopol. The complexation between Carbopol and enrofloxacin was confirmed by turbidity, UV spectrophotometry, wide angle X-ray diffraction, and differential scanning calorimetry. The enrofloxacin content in the complexes was 34% (Carbo-enrofloxacin complex I) and 57% (Carbo-enrofloxacin complex II) depending on the preparation method. The dissolution rate of enrofloxacin from the complex increased as the pH was reduced. The dissolution rate of enrofloxacin from the Carbo-enrofloxacin complex I was significantly lower than that of the enrofloxacin powder. Therefore, these observations suggest that Carbo-enrofloxacin complex I can be used to mask the taste of enrofloxacin.     

Simultaneous extraction of enrofloxacin and ciprofloxacin from chicken tissue by molecularly imprinted matrix solid-phase dispersion

An ofloxacin molecularly imprinted polymer was synthesized and used as a dispersant of matrix solid-phase dispersion for the determination of enrofloxacin and ciprofloxacin in chicken tissue. The selected dispersant shows high affinity to enrofloxacin and ciprofloxacin in aqueous environment and could selectively enrich them from chicken tissue matrix. The extract was sufficiently clean for further chromatographic analysis without interferences from template leakage or chicken tissue matrix. Linearity ranged from 0.03 to 200 μg/g with the correlation coefficient r² > 0.9993. The recoveries of spiked chicken tissues were in the range of 82.7–96.6% for enrofloxacin and 88.7–102% for ciprofloxacin.     

Effects of inducers of cytochrome P450s on enrofloxacin N-deethylation in crucian carp Carassius auratus gibelio

In this study with crucian carp (Carassius auratus gibelio), the effect on enrofloxacin (EF) and its metabolite ciprofloxacin (CF) and on the activity of cytochrome P450 1A (CYP1A) and cytochrome P450 3A (CYP3A) was estimated following the oral administration of rifampicin (RIF) (12 mg/kg) and β-naphthoflavone (BNF) (12 mg/kg), respectively. First, reversed-phase high-performance liquid chromatography (RP-HPLC) was used to detect the pharmacokinetics of EF with continual blood sampling. In RIF-treated, BNF-treated and control groups, the value of the C_maxCF/C_maxEF ratio was 4.41, 0.81 and 0.95, and the corresponding value of the AUC_0-t-CF/AUC_0-t-EF ratio was 3.69, 1.84 and 1.76, respectively. In the RIF-treated, BNF-treated and control groups, the MRT values of EF were 26.57, 27.45 and 30.88 h, and the corresponding values for CF were 5.79, 35.18 and 38.11 h, respectively. Based on these results for crucian carp, the accumulation and elimination of EF and CF in the RIF-treated group were more rapid than in BNF-treated and control groups. Second, liver microsomes were pretreated with the inducer of CYP1A for BNF and that of CYP3A for RIF, and then the enzymatic activities of CYP1A and CYP3A were measured, respectively. The activities of ethoxyresorufin-O-deethylation (EROD) and erythromycin-N-demethylation (ERND) increased significantly (P < 0.05) for CYP1A and CYP3A, respectively. However, in further experiments on the formation of CF, the level of EF N-deethylation was significantly induced by RIF and inhibited by ketoconazole (KTZ) for CYP3A but had no influence for CYP1A, BNF and berberine chloride (BER). We concluded that CYP3A might be responsible for the N-deethylation of EF and because of this activity, could also serve as a toxicity biomarker in crucian carp.     

The effect of a commercial competitive exclusion product on the selection of enrofloxacin resistance in commensal E. coli in broilers

The effect of a competitive exclusion product (Aviguard®) on the selection of fluoroquinolone resistance in poultry was assessed in vivo in the absence or presence of fluoroquinolone treatment.

Two experiments using a controlled seeder-sentinel animal model (2 seeders: 4 sentinels per group) with one-day-old chicks were used. For both experiments, as soon as the chicks were hatched, the birds of two groups were administered Aviguard® and two groups were left untreated. Three days later, all groups were inoculated with an enrofloxacin-susceptible commensal E. coli strain. Five days after hatching, two birds per group were inoculated with either a bacteriologically fit or a bacteriologically non-fit enrofloxacin-resistant commensal E. coli strain. In experiment 2, all groups were orally treated for three consecutive days (days 8–10) with enrofloxacin. Throughout the experiments, faecal excretion of all inoculated E. coli strains was determined on days 2, 5, 8, 11, 18 and 23 by selective plating (via spiral plater). Linear mixed models were used to assess the effect of Aviguard® on the selection of fluoroquinolone resistance.

The use of Aviguard® (P?E. coli when no enrofloxacin treatment was administered. However, this beneficial effect disappeared (P?=?0.37) when the birds were treated with enrofloxacin. Similarly, bacterial fitness of the enrofloxacin-resistant E. coli strain used for inoculation had an effect (P?P?=?0.70).

Thus, enrofloxacin treatment cancelled the beneficial effects from administrating Aviguard® in one-day-old broiler chicks and resulted in an enrofloxacin-resistant flora.

RESEARCH HIGHLIGHTS

• The effect of Aviguard® on the selection of enrofloxacin resistance was assessed in vivo.

• Without enrofloxacin, Aviguard® reduced the selection of enrofloxacin resistance.

• When enrofloxacin was administered, it cancelled the beneficial effect of Aviguard®.

     

高效液相色谱荧光检测法同时测定婴幼儿食用鱼粉中环丙沙星和恩诺沙星残留量

目的:建立用高效液相色谱荧光检测器同时测定婴幼儿食用鱼粉中环丙沙星和恩诺沙星残留的方法。方法:试样经水复原后,由5%乙酸乙腈提取,正己烷脱脂,以0.05 mol/L磷酸三乙胺缓冲液-乙腈(体积比为85∶15)为流动相洗脱,荧光检测器定性定量。结果:该方法对测定的两种药物的检出限均为5μg/kg,定量限均为10μg/kg。两种药物在5μg/L~80μg/L范围内线性关系良好,相关系数均大于0.99。在添加水平分别为10μg/kg、20μg/kg和80μg/kg时,两种药物的加标回收率为80.3%~92.6%,相对标准偏差(RSD)为1.2%~3.8%。结论:方法操作简单、重现性好、灵敏度高、分析时间短,适用于鱼粉中环丙沙星和恩诺沙星残留的确证检测。     

HPLC residues of enrofloxacin and ciprofloxacin in eggs of laying hens

Eggs of 12 laying hens with 5 mg/kg/day oral administration of 5% enrofloxacin (EFX) or ciprofloxacin (CFX) solution during 5 days contained residues from 0.02 to 1.98 μg/g (EFX) or 0.14 to 0.28 μg/g (CFX). At identical dosage regime High Performance Liquid Chromatograhy (HPLC) residues of EFX were 6-fold greater than CFX ones. Maximun concentrations were detected at the second day after the administration withdrawal. The limits of detection were 0.019 μg/g for EFX and 0.156 μg/g for CFX. The recovery was 36–50% for CFX and 49–85% for EFX. The withdrawal treatment periods in hens are six days for EFX and five days for CFX in order to avoid violative levels of egg residues.