Pharmacokinetics of norfloxacin after intravenous, intramuscular and subcutaneous administration to rabbits.

The disposition kinetics of norfloxacin, after intravenous, intramuscular and subcutaneous administration was determined in rabbits at a single dose of 10 mg/kg. Six New Zealand white rabbits of both sexes were treated with aqueous solution of norfloxacin (2%). A cross-over design was used in three phases (2 × 2 × 2), with two washout periods of 15 days. Plasma samples were collected up to 72 hr after treatment, snap-frozen at -45°C and analysed for norfloxacin concentrations using high-performance liquid chromatography. The terminal half-life for i.v., i.m. and s.c. routes was 3.18, 4.90 and 4.16 hr, respectively. Clearance value after i.v. dosing was 0.80 L/h·kg. After i.m. administration, the absolute bioavailability was (mean ± SD) 108.25 ± 12.98% and the Cmax was 3.68 mg/L. After s.c. administration, the absolute bioavailability was (mean ± SD) 84.08 ± 10.36% and the Cmax was 4.28 mg/L. As general adverse reactions were not observed in any rabbit and favourable pharmacokinetics were found, norfloxacin at 10 mg/kg after i.m. and s.c. dose could be effective in rabbits against micro-organisms with MIC ≤0.14 or 0.11 µg/mL, respectively.

Investigation and Optimization of the Effect of Polymers on Drug Release of Norfloxacin from Floating Tablets.

BACKGROUND: Norfloxacin is fluoroquinolone anti-infective used in the treatment of urinary tract infections, prostatitis, gonorrhea and genital tract infections. It has plasma half life of 3 to 4 h requiring multiple dosing in the treatment. Releaseretarding polymers can be used to modulate the drug release of norfloxacin. OBJECTIVES: The objective of this study was to investigate the effect of release-retarding polymers on the drug release of norfloxacin from floating tablets. MATERIAL AND METHODS: Norfloxacin was procured as a gift sample from Concept Pharma Ltd. Aurangabad (India) and HPMC K100M was procured as a gift sample from Colorcon Asia Pvt. Ltd., Goa (India). The tablets were prepared by direct compression method and various pharmaceutical parameters were evaluated. RESULTS: It was observed that all tablet formulations F1-F9 retained the drug release up to 12 h with good floating property but only Batch-F4 complies with the USP dissolution limits with a minimum floating lag time. The drug release kinetics were evaluated by the model-dependent (curve fitting) method using PCP Disso v3 software shows Batch-F4 shows to best fit with Peppas model for which R2 value was 0.9921 and the release exponent value was 0.6892. CONCLUSIONS: The drug release kinetics study indicates that the floating tablets release the drug by diffusion followed by erosion mechanism. Obtained in-vitro drug release data was analyzed by design expert software for drug release at first hour and at 12th h values and found that release the selected independent variables like HPMC K100M and sodium alginate concentration has a significant effect on drug release.

Comparative pharmacokinetics of norfloxacin nicotinate in common carp (Cyprinus carpio) and crucian carp (Carassius auratus) after oral administration.

Comparative pharmacokinetics of norfloxacin nicotinate (NFXNT) was investigated in common carp (Cyprinus carpio) and crucian carp (Carassius auratus) after a single oral dose of 10 mg/kg body weight (b.w.). Analyses of plasma samples were performed using ultra-performance liquid chromatography (UPLC) with fluorescence detection. After oral dose, plasma concentration-time curves of common carp and crucian carp were best described by a two-compartment open model with first-order absorption. The pharmacokinetic parameters of common carp were similar to those of crucian carp. The distribution half-life (t1/2α ), elimination half-life (t1/2ß ), peak concentration (Cmax ), time-to-peak concentration (Tmax ), and area under the concentration-time curve (AUC) of common carp were 1.58 h, 26.33 h, 6069.79 µg/L, 1.08 h, and 103072.36 h·µg/L, respectively, and those corresponding to crucian carp were 1.36 h, 26.55 h, 9586.06 µg/L, 0.84 h, and 126604.4 h·µg/L, respectively. These studies demonstrated that 10 mg NFXNT/kg body weight in common carp and crucian carp following oral dose presented good pharmacokinetic characteristics.

Experimental and theoretical studies on the molecular properties of ciprofloxacin, norfloxacin, pefloxacin, sparfloxacin, and gatifloxacin in determining bioavailability.

The aim of this investigation is to identify, by in silico and in vitro methods, the molecular determinants, e.g., solubility in an aqueous medium and lipophilic properties, which have an effect on the bioavailability of five selected fluoroquinolones. These properties were estimated by analysis of the electrostatic potential pattern and values of free energy of solvation as well as the partition coefficients of the studied compounds. The study is based on theoretical quantum-chemical methods and a simple experimental shake-flask technique with two immiscible phases, n-octanol and phosphate buffer. The solvation free energy values of compounds in both environments appeared to be negative. The wide range of electrostatic potential from negative to positive demonstrates the presence of dipole-dipole intermolecular interactions, while the high electron density at various sites indicates the possibility of hydrogen bond formation with solvent molecules. High partition coefficient values, obtained by summing the atomic contributions, did not take various correction factors into account and therefore were not accurate. Theoretical partition coefficient values based on more accurate algorithms, which included these correction factors (fragmental methods), yielded more accurate values. Theoretical methods are useful tools for predicting the bioavailability of fluoroquinolones.

Molecular analysis of antimicrobial agent translocation through the membrane porin BpsOmp38 from an ultraresistant Burkholderia pseudomallei strain.

Burkholderia pseudomallei (Bps) is a Gram-negative bacterium that causes melioidosis, an infectious disease of animals and humans common in northern and north-eastern parts of Thailand. Successful treatment of melioidosis is difficult due to intrinsic resistance of Bps to various antibacterial agents. It has been suggested that the antimicrobial resistance of this organism may result from poor permeability of the active compounds through porin channels located in the outer membrane (OM) of the bacterium. In previous work, a 38-kDa protein, named "BpsOmp38", was isolated from the OM of Bps. A topology prediction and liposome-swelling assay suggested that BpsOmp38 comprises a ß-barrel structure and acts as a general diffusion porin. The present study employed black lipid membrane (BLM) reconstitution to demonstrate the single-channel conductance of the trimeric BpsOmp38 to be 2.7±0.3 nS in 1M KCl. High-time resolution BLM measurements displayed ion current blockages of seven antimicrobial agents in a concentration-dependent manner with the translocation on-rate (kon) following the order: norfloxacin≫ertapenem>ceftazidime>cefepime>imipenem>meropenem>penicillin G. The dwell time of a selected antimicrobial agent (ertapenem) decayed exponentially with increasing temperature. The energy barrier for the ertapenem binding to the affinity site inside the BpsOmp38 channel was estimated from the Arrhenius plot to be 12 kT and for the ertapenem release to be 13 kT at +100 mV. The BLM data obtained from this study provide the first insight into antimicrobial agent translocation through the BpsOmp38 channel.

Mutation in the sdeS gene promotes expression of the sdeAB efflux pump genes and multidrug resistance in Serratia marcescens.

Serratia marcescens gained resistance to both biocides and antibiotics on expressing the SdeAB efflux pump, following exposure to increasingly higher concentrations of a biocide (H. Maseda et al., Antimicrob. Agents Chemother. 53:5230-5235, 2009). To reveal the regulatory mechanism of sdeAB expression, wild-type cells were subjected to transposon-mediated random mutagenesis, and a mutant with antibiotic resistance, which mimicked the phenotype of the previous biocide-resistant cells, was obtained. The transposon element was found in the chromosomal DNA downstream of the sdeAB operon. Sequencing revealed the presence of an open reading frame (ORF) encoding a protein with 159 amino acid residues that is highly similar to the BadM-type transcriptional repressor, designated sdeS. The level of sdeB::xylE reporter gene expression, undetectable in the wild-type cells, appeared to be fully comparable to that in the biocide-resistant cells. Nucleotide sequencing of the mutant revealed sdeS to have a single G-to-A base substitution at position 269 that converted Trp90 to a stop codon. Introduction of a plasmid-borne intact sdeS into the mutant cells and the biocide-resistant cells resulted in a reduction in sdeB::xylE reporter activity to an undetectable level. These results suggested that SdeS functions as a repressor of the sdeAB operon. It was concluded that the original biocide-resistant cells had an impaired sdeS and, therefore, a derepressed level of the SdeAB efflux pump.

Synthesis and biodistribution of a novel (99m)TcN complex of norfloxacin dithiocarbamate as a potential agent for bacterial infection imaging.

Achieving a (99m)Tc-labeled fluoroquinolone derivative as a single photon emission computed tomography (SPECT) tracer is considered to be of great interest. The norfloxacin dithiocarbamate (NFXDTC) was synthesized and radiolabeled with a [(99m)TcN]²(+) intermediate to form the (99m)TcN-NFXDTC complex in high yield. The radiochemical purity of (99m)TcN-NFXDTC was over 90%, as measured by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC), without any notable decomposition at room temperature over a period of 6 h. The partition coefficient and electrophoresis results indicated that (99m)TcN-NFXDTC was lipophilic and neutral. The bacterial binding assay studies showed tht (99m)TcN-NFXDTC had a good binding affinity. Biodistribution results in bacterial infected mice showed that (99m)TcN-NFXDTC had a higher uptake at the sites of infection and better abscess/blood and abscess/muscle ratios than those of (99m)Tc-ciprofloxacin and (99m)TcN-CPFXDTC (CPFXDTC = ciprofloxacin dithiocarbamate). The biodistribution results of (99m)TcN-NFXDTC in bacterially infected mice and in mice with turpentine-induced abscesses indicated that (99m)TcN-NFXDTC was suited to be a bacteria-specific infection imaging agent. Single photon emission computed tomography (SPECT) image studies showed there was a visible accumulation in infection sites, suggesting that it would be a promising candidate for bacterial infection imaging.

A simple chromatographic method for determining norfloxacin and enoxacin in pharmacokinetic study assessing CYP1A2 inhibition.

We developed a simple assay method for the determination of serum and urine norfloxacin and enoxacin using reversed-phase high-performance liquid chromatography and perchloric acid precipitation for sample pre-treatment. Optimized conditions can permit detection of norfloxacin and enoxacin in the same chromatogram, so either compound can be used as an internal standard for another determinant. Supernatants of the precipitated samples were analyzed by the octadecylsilyl silica-gel column under ambient temperature and an ultraviolet wavelength of 272 nm. A mobile phase solvent consisting of 20 mm sodium dihydrogenphosphate (pH 3.0) and acetonitrile (85:15, v/v) was pumped at a flow rate of 1.0 mL/min. The calibration curves for norfloxacin and enoxacin at a concentration of 62.5-1000 ng/mL for serum and 250-4000 ng/mL for urine were linear (r > 0.9997). The recoveries of norfloxacin and enoxacin from serum and urine were >94% with the coefficient of variations (CV) <5%. The CVs for intra- and inter-day assay of norfloxacin and enoxacin were <4.2 and <5.5%, respectively. This method can be applied to the pharmacokinetic study of norfloxacin and enoxacin after repeated administration to assess changes in CYP1A2 activity in healthy subjects.

[Study on the inhibit mechanism primarily of extracts from Coptis on clinical resistant the medicine of Staphylococcus aureus].

OBJECTIVE: To discuss the inhibit mechanism primarily of extracts from Coptis on clinical resistant the medicine of Staphylococcus aureus. METHODS: Used SDS-PAGE electrophoresis, spectrophotometry and semiautomatic biochemistry analysis to detect the accumulated concentration of norfloxacin, membranin electrophoretogram and the enzymatic activity in extracellular fluid before and after Coptis extract disposition. RESULTS: The accumulated concentration of medicine norfloxacin within the experiment strains which treated with Coptis extract was clear higher than that of the blank space (P < 0.01); some proteins which molecular weights were in 35 - 38 kDa rebound expressed after Coptis extract treated; The extracellular fluid enzymic activities of resistant Staphylococcus aureus had no significant difference (P > 0.05). CONCLUSION: The inhibit mechanism primarily of extracts from Coptis on clinical resistant the medicine of Staphylococcus aureus is the results of the combined action of various chemical composition and multi-target interaction, and the exact molecular mechanism remains to be further researched.

Bioequivalence evaluation of norfloxacin tablets based on in vitro - in vivo correlation.

Present study was designed to establish in-vitro and in-vivo correlation (IVIVC) of two immediate release tablet formulations of 400mg Norfloxacin [Drug A as test and Drug B as reference]. Dissolution study was conducted in 0.1 N HCl using USP apparatus II. In-vivo evaluation was carried out in 18 healthy humans according to a single dose, two-sequence, and cross-over randomized with a wash-out period of one week. After dosing, serial blood samples were collected for a period of 10 hours. Plasma harvested from blood, was analyzed for norfloxacin by a sensitive, reproducible and accurate HPLC method. Various pharmacokinetic parameters were determined from plasma concentrations for both the formulations. Non-significant difference was found for test/reference ratio of these parameters and the value of F was found to be 0.99 which is in good agreement with the limits given in FDA and WHO guidelines for such parameters. Difference factor (f(1)), similarity factor (f(2)) and level A IVIVC were evaluated showing that drug A is bioequivalent to drug B.

[Development of Prediction System for Drug Absorption after Intranasal Administration Incorporating Physiologic Functions of Nose -Estimation of in Vivo Drug Permeation through Nasal Mucosa Using in Vitro Membrane Permeability].

The nasal drug application has drawn much attention as the strategy for the delivery route of many drug modalities such as the poorly absorbed drugs, peptides, nucleic acid, and central nervous system drugs. The absorption of drug after intranasal (IN) application depends on the nasal residence time of applied drug, affected by mucociliary clearance (MC). MC is a decisive factor in the nasal absorption of drug. We describe the establishment of in vitro evaluation system of nasal MC via the moving velocity of a marker particle on nasal mucosa, and the development of the pharmacokinetic model to which in vitro parameters on nasal MC was incorporated to enable the prediction of drug absorption after IN application. Moreover, the pharmacokinetics of norfloxacin after IN application was investigated using MC-modified rats pretreated with MC modulators. Nasal absorption fluctuated due to changes in the nasal residence time of drug in response to changes in MC. The prediction system enables quantitative evaluation of changes in drug absorption associated with MC fluctuations. In addition, for a precise prediction system for drug absorption after IN application from the drug absorption model, the relationships between in vitro drug permeability through Calu-3 layers, in vivo transnasal permeation of drug and in vivo bioavailability after IN application were evaluated. The significant correlations between these parameters were obtained, suggesting that transnasal permeability and drug absorption after IN application can be predicted from in vitro membrane permeability.

Co-delivery of norfloxacin and tenoxicam in Ag-TiO2/poly(lactic acid) nanohybrid.

A nanohybrid formulation of silver­titanium dioxide nanoparticles/poly(lactic acid) (Ag-TiO2/PLA) was designed for Norfloxacin/Tenoxicam (NOR/TENO) targeted delivery to maximize the bioavailability and minimize the side effects of the drugs. Ag-TiO2 nanoparticles were prepared via Stober method. NOR, TENO and a mixture of NOR/TENO (NT) were loaded onto Ag-TiO2 nanoparticles and coated by PLA via solution casting. The physical interaction between the drugs and carrier was confirmed by Fourier-transform infrared (FTIR) analysis. X-ray diffraction (XRD) demonstrated that Ag-TiO2 consists of a cubic phase of Ag with two phases of TiO2 (anatase and brookite). Ag nanoparticle fine spots coated with TiO2 were collected to form spheres averaging at 100 nm in size. In-vitro release behavior of drugs was studied at different pH (5.4, 7.4) and the release of drug from NT/Ag-TiO2/PLA was faster at pH 7.4. Gram-positive and Gram-negative bacteria were used to investigate antibacterial properties of the nanohybrid. Cytotoxicity of the nanohybrid using an MTT assay was studied against different tumor and normal cell lines. It was found that NT/Ag-TiO2/PLA has an excellent cytotoxic effect against various bacterial cells and tumor cell lines. In addition, antioxidant properties of the nanohybrids were tested using ABTS method and the nanohybrid showed moderate antioxidant activity.

Synthesis and Design of Norfloxacin drug delivery system based on PLA/TiO2 nanocomposites: Antibacterial and antitumor activities.

Biodegradable, biocompatible and non-toxic polymer-based nanoparticles are the novel nanotherapeutic tool which is used for adsorption and encapsulation drugs. Extended release formulation of Norfloxacin antibiotic, chemotherapeutic agent model, drug in the form of encapsulated and loaded poly (lactic acid) nanocomposites-based Titanium dioxide (PLA/TiO2) was developed. Nanocomposites were prepared using different contents (1, 3, 5 wt %) and morphologies of TiO2 (spheres (S), rods (R). The dispersion of TiO2 was aided by ultrasonic technique followed by solution casting method. The morphology, particle size, crystallite size and composition of the nanocomposites were examined by SEM, TEM, XRD and FTIR. The crystallinity and thermal behavior of the nanocomposites were characterized by DSC and TGA. NOR was loaded onto TiO2 nanospheres (NOR@TiO2 (S)) and the optimum conditions for loading was investigated. Pseudo-second order model was the more adequate to represent the kinetic data. The equilibrium data followed Freundlich adsorption isotherm and the adsorption process was exothermic. NOR@TiO2 (S) was encapsulated into PLA and in vitro release behavior of drug was compared with NOR adsorbed into PLA (NOR@PLA) and nanocomposites (NOR@PLA/TiO2) using different pH (6.7, 7.4) media. To study the mechanism of NOR release, first order, Higuchi, Hixon Crowell and Korsmeyer-Peppas models were applied on the experimental results. The cytotoxicity of the loaded nanocomposites using MTT assay was studied against HepG 2, MCF-7, HCT 116, PC-3, Hela, WI-38 and WISH cells. The encapsulated (NOR@ 5S/En PLA) showed the highest cytotoxic efficacy with moderate effect on normal cells. Moreover, the nanocomposites have great potential against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Salmonella and Klebsiella pneumonia. NOR@ PLA/TiO2 nanocomposites showed better antibacterial efficacy than NOR encapsulated nanocomposites. The nanocomposites could be effective vehicles for the sustained delivery of toxic anticancer drug.

Development and evaluation of gastroretentive norfloxacin floating tablets.

Floating matrix tablets of norfloxacin were developed to prolong gastric residence time, leading to an increase in drug bioavailability. Tablets were prepared by the wet granulation technique, using polymers such as hydroxypropyl methylcellulose (HPMC K4M, HPMC K100M) and xanthan gum. Tablets were evaluated for their physical characteristics, viz., hardness, thickness, friability, and mass variation, drug content and floating properties. Further, tablets were studied for in vitro drug release characteristics for 9 hours. The tablets exhibited controlled and prolonged drug release profiles while floating over the dissolution medium. Non-Fickian diffusion was confirmed as the drug release mechanism from these tablets, indicating that water diffusion and polymer rearrangement played an essential role in drug release. The best formulation (F4) was selected based on in vitro characteristics and was used in vivo radiographic studies by incorporating BaSO4. These studies revealed that the tablets remained in the stomach for 180 +/- 30 min in fasting human volunteers and indicated that gastric retention time was increased by the floating principle, which was considered desirable for the absorption window drugs.

Determination of norfloxacin in urine and pharmaceutical samples using terbium doped zinc sulphide nanomaterials-sensitized fluorescence method.

Highly crystalline polyethylene glycol (PEG) coated Tb3+ doped ZnS nanoparticles have been synthesized and successfully used for norfloxacin sensing. The crystallographic and morphological analyses of PEG coated Tb3+ doped ZnS nanoparticles were performed by X-ray diffraction and Transmission electron microscopy, respectively. The confirmation of Tb3+ doping in ZnS host matrix was done by emission spectroscopy and energy dispersive X-ray spectroscopy. Further, the interaction of norfloxacin with PEG coated Tb3+ doped ZnS nanomaterials was confirmed by optical analysis: spectrophotometrically and spectrofluorimetrically. Norfloxacin sensing was measured by luminescence intensity which increased with increase in concentration of norfloxacin in range from 2.0 × 10-9-8.0 × 10-7 mol L-1, with its correlation coefficient 0.9991. The detection limit of proposed method was 0.05 × 10-9 mol L-1. The developed luminescence method was successfully applied for the determination of norfloxacin using PEG coated Tb3+ doped ZnS nanoparticles in urine and pharmaceutical samples.

Comparative study of the antimutagenic properties of vitamins C and E against mutation induced by norfloxacin.

BACKGROUND: Norfloxacin like other fluoroquinolones, is known to mbe mutagenic for Salmonella typhimurium TA102 strain. This mutagenic effect is due to free oxygen radicals (ROS), because it is inhibited by antioxidants such as beta-carotene and naturally occurring antioxidants of Roheo discolor and other plants. The aim of this work was to evaluate combination therapy with norfloxacin and vitamins C and E, to reduce the possible genotoxic risk associated with fluoroquinolones. METHOD: The antimutagenicity of alpha-tocoferol (Vitamin E) and ascorbic acid (Vitamin C) against norfloxacin-induced mutation was evaluated on S. typhimurium TA102, using the aroclor-1254-induced S9 rat liver homogenate. The minimum inhibitory concentration (MIC) a measure of the bactericidal effect of norfloxacin, was obtained in vitro by the plate dilution method. RESULTS: Vitamin E (0.5 mg per Petri dish) induced a statistically significant reduction (P < 0.001) in the mutagenicity of norfloxacin, whereas Vitamin C (1 mg per Petri dish) had no such effect. Neither of these vitamins altered the MIC for norfloxacin against 25 uropathogenic strains of Escherichia coli. CONCLUSION: These results suggest that Vitamin E is a potent antimutagen that would be worthwhile being used in conjunction with fluoroquinolone treatment. The minimal antimutagenic effect of Vitamin C observed under these experimental conditions may have been because Vitamin C in the Ames test induces a Fenton reaction, and if divalent cations are present, it can act as a pro-oxidant rather than an antioxidant. Ascorbic acid should be further evaluated in the presence of different divalent cations concentrations.

Ocular gelling microspheres: in vitro precorneal retention time and drug permeation through reconstituted corneal epithelium.

PURPOSE: The model drug norfloxacin (NOR) was encapsulated into trehalose (TRH) and hydroxyethylcellulose (NAT) microspheres to obtain a novel gelling ophthalmic delivery system for prolonged release on corneal tissue. METHODS: We assessed NOR release from microspheres, prepared by the emulsion-solvent evaporation method. A new in vitro tear turnover model, including inserts containing reconstituted human corneal epithelium (RHC), was designed to evaluate the TRH/NAT microspheres' precorneal retention time. Bioadhesive properties of TRH/NAT microspheres were validated by using drug-loaded microspheres prepared with gelatine (GLT) commonly used as reference material in adhesion studies. RESULTS: In vitro drug release showed a typical trend of swelling systems. Precorneal retention tests showed that TRH/NAT microspheres maintained fluorescence in tear fluid for 81.7 min, whereas TRH/GLT microspheres and water solution maintained fluorescence for 51.8 and 22.3 min, respectively. NOR released from microspheres permeated throughout RHC slower (J(s) = 23.08 microg/cm(2)h) than NOR from commercial eye drops (J(s) = 42.77 microg/cm(2)h) used as the control. CONCLUSIONS: Adequate drug concentrations in aqueous humor could be prolonged after the administration of TRH/NAT/NOR microspheres. Good bioadhesive properties of the system and slow drug release on corneal surface might increase ocular NOR bioavailability.

Pharmacokinetic Profile of Norfloxacin in Pigeons / Perfil Farmacocinético da Norfloxacina em Pombos

Through this work, the pharmacokinetics of Norfloxacin in pigeons were explored by using six healthy male pigeons as the subjects for this study. The pharmacokinetic indices of orally administered Norfloxacin were obtained by microbiological assay and then the data were fitted to the two-compartment pharmacokinetic open model to evaluate the distribution and excretion parameters.In the achieved results, the calculated absorption rate constant (Kab) was 1.26 h-1, the maximum achieved concentration of Norfloxacin was 2.75 µg/ml at 1.34 hr., the volume of distribution (Vd/F) was 3.15 L/kg.The half-life (t1/2ß) was 4.9 hrs., the calculated area under the curve of Norfloxacin (AUC0-t) was 16.75 (h*µg)/ml, while the clearance of Norfloxacin (Cl/F) was 0.49 L/hr/kg.In conclusion, the pharmacokinetic parameters of Norfloxacin in pigeons are not far away from other birds like chickens, considering the differences among them. Norfloxacin is a valuable antibacterial agent against susceptible bacterial infections depending on the obtained pharmacokinetic profile.(AU)

Através deste trabalho, a farmacocinética da Norfloxacina em pombos foi explorada usando seis pombos machos saudáveis como sujeitos para este estudo. Os índices farmacocinéticos da norfloxacina, administrada por via oral, foram obtidos por ensaio microbiológico e, em seguida, os dados foram ajustados ao modelo aberto de farmacocinética de dois compartimentos para avaliar os parâmetros de distribuição e excreção. Nos resultados obtidos, a taxa constante de absorção (Kab) calculada foi de 1,26 h-1, a concentração máxima alcançada da Norfloxacina foi de 2,75 µg/ml em 1,34 h, o volume de distribuição (Vd/F) foi de 3,15 L/kg. A meia-vida (t1/2ß) foi de 4,9 h, a área calculada sob a curva de concentração da Norfloxacina (AUC0-t) foi de 16,75 (h*µg)/ml, enquanto a depuração da Norfloxacina (Cl/F) foi de 0,49 L/h/kg. Em conclusão, os parâmetros farmacocinéticos da Norfloxacina em pombos não estão muito longe de outras aves, como galinhas, considerando as diferenças entre eles. A norfloxacina é um agente antibacteriano valioso contra infecções bacterianas susceptíveis, dependendo do perfil farmacocinético obtido.(AU)

Cyclodextrin based nanosponge of norfloxacin: Intestinal permeation enhancement and improved antibacterial activity.

Nanosponges are a novel class of hyperbranched cyclodextrin-based nanostructures that exhibits remarkable potential as a drug host system for the improvement in biopharmaceutical properties. This work aims the development of cyclodextrin-based nanosponge of norfloxacin to improve its physicochemical characteristics. ß-cyclodextrin was used as base and diphenyl carbonate as crosslinker agent at different proportions to produce nanosponges that were evaluated by in vitro and in vivo techniques. The proportion cyclodextrin:crosslinker 1:2 M/M was chosen due to its higher encapsulation efficiency (80%), revealing an average diameter size of 40 nm with zeta potential of -19 mV. Norfloxacin-loaded nanosponges exhibited higher passage of norfloxacin in comparison to norfloxacin drug alone by Ussing chamber method. The nanosponge formulation also revealed a mucoadhesive property that could increase norfloxacin absorption thus improving its antibiotic activity in an in vivo sepsis model. Therefore, nanosponges may be suitable carrier of norfloxacin to maximize and facilitate oral absorption.

Synthesis, Characterization and Antimicrobial Evaluation of Lipid Based Norfloxacin Prodrug.

BACKGROUND: Fluoroquinolones, the synthetic antibacterial agents are being successfully utilized against bacterial infections, since the time immemorial. Despite of enormous useful features, these drugs are associated with some limitations also. Large number of efforts has been made by various scientists to improve pharmacokinetic properties of these drugs and hence, to overcome the limitations associated with them. OBJECTIVES: The aim of this paper is to introduce a novel scheme for synthesis of prodrug with improved pharmacokinetic properties i.e., lipophilicity and consequently, modified bioavailability of norfloxacin. METHODS: Fatty acid hydrazide of selected fatty acid was synthesized followed by preparation of 5-formyl salicylamide. N-Mannich base of norfloxacin was synthesized by reacting norfloxacin with 5-formyl salicylamide. The prodrug was obtained by covalently coupling this N-Mannich base of norfloxacin with fatty acid hydrazide. The synthesized lipid based prodrug was evaluated for partition coefficient by shake flask method and screened for antimicrobial activity against selected strains. Drug content determination and in vitro dissolution studies utilizing HPLC were also carried out. RESULTS: The synthesized prodrug was found to exhibit improved partition coefficient (1.15) when compared with parent drug, norfloxacin (0.46). The results of antimicrobial evaluation indicate promising antibacterial and antifungal activity. CONCLUSION: The synthesized prodrug proved to be a good antimicrobial substance due to improved lipophilicity and would be expected to be used as a suitable candidate for exploration of possible utilities in treatment of bacterial infections in forthcoming time.