• Journal of Pharmaceutical Investigation
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• 제25권3호
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• pp.265-270
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• 1995

The pharmacokinetics of norfloxacin (100 mg/kg, oral) in renal failure rabbits was studied. Renal failure rabbits were induced by the i.v. injection of folate (50,100 and 150 mg/kg). These produced significant increases of serum creatinine concentration $(S_{cr})$ and blood urea nitrogen (BUN). Plasma concentration and AUC of norfloxacin significantly increased. Elimination rate constant $(K_{el})$ of norfloxacin significantly decreased, and half-life $(t_{1/2})$ of norfloxacin significantly increased. Correlation between serum creatinine concentration $(S_{cr})$ and half-life $(t_{1/2})$ of norfloxacin, and correlation between BUN and AUC of norfloxacin have linear relationship respectively. These results suggest that adjustment or the dosage regimen of norfloxacin is desirable, and serum creatinine concentration $(S_{cr})$ as well as BUN can be used an index for adjusting the dosage regimen of norfloxacin in renal failure.

• Journal of Pharmaceutical Investigation
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• 제17권1호
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• pp.1-14
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• 1987

To increase the bioavailability of norfloxacin, inclusion complex of antimicrobial agent norfloxacin with ${\beta}-Cyclodextrin$ was prepared and studied by the solubility method, spectrophotometric methods(UV, IR, $^1H-NMR$), differential thermal analysis, powder X-ray diffractometry, the physical properties, the antimicrobial activity, DNA binding and in situ recirculation technique. The conclusions are summerized as following; 1) The inclusion complexation was identified by means of solubility, spectrophotometry(UV, IR, NMR), DTA and X-ray diffraction. 2) The molar ratio of $norfloxacin-{\beta}-cyclodextrin$ complex was 1 : 1. 3) The stability constant of $norfloxacin-{\beta}-cyclodextrin$ complex was $21.5\;M^{-1}$, and both true and apparent partition coefficients of the inclusion complex were larger than those of norfloxacin. 4) The time required to dissolve 60% $(T_{60}%)$ of the inclusion complex was 120 min. in distilled water and in the artificial intestinal juice, while norfloxacin did not reach to 60% dissolution within 120 min. 5) The antimicrobial activity of the inclusion complex against Pseudomonas aeruginosa, Klebsiella pneumoniae and Staphylococcus aureus showed no significant difference compared to that of norfloxacin alone. 6) Studies on binding properties between the inclusion complex and norfloxacin alone to DNA according to equilibrium dialysis showed no significant differency. 7) In situ absorption rates (Ka) of inclusion complex and norfloxacin alone were 0.229 and $0.102hr^{-1}$, respectively.

• 약학회지
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• 제43권4호
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• pp.442-446
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• 1999

The synthesis and antimicrobial activity of N-substituted glycyl derivatives of Norfloxacin were described. Norfloxacin was treated with chloroacetyl chloride to yield chloroacetyl norfloxacin (1). This compounds was treated with alkylamines to obtain quinolone carboxylic acids (2-6), which were reacted with pivaloyloxymethyl chloride to get pivaloyloxymethyl quinolone carboxylates (7-11). Free carboxylic quinolones (2-6) showed little stronger activities to their pivaloyloxymethyl esters (7-11). In quinolone analogues, longer alkyl chain compounds showed stronger activities than shorter one.

• 대한화학회지
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• 제44권1호
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• pp.4-9
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• 2000

여러 가지의 분광법과 전위차 적정법을 이용하여, 퀴놀론의 유도체인 norfloxacin의 자체 회합과 pH에 따른 형태에 대하여 연구하였다. norfloxacin의 작용기 중에서 피페라진 고리와 카르복실기의 두 질소원자는 낮은 pH 용액에서는 수소화(양이온 형태)되고, 높은 pH 용액에서는 두 수소가 모두 이탈하며(음이온 형태), 중간 pH 범위의 용액에서는 zwitter 이온이 두드러지게 형성되었다. 또한, 이 중간 pH용액에서는 norfloxacin 두 분자가 자체 회합을 이루었다. Stern-Volmer 측정법에 의하여 norfloxacin-DNA 결합체의 결합 상수를 조사하였는데, 용액의 pH가 낮을수록 그 결합 상수는 증가하였다. 이것은 용액 상태에서 DNA에 결합하는 norfloxacin의 분자종이 여러 분자종 중에서 그 형태가 양이온임을 나타내는 것이다.

• Bulletin of the Korean Chemical Society
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• 제19권4호
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• pp.449-457
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• 1998

We compared various spectroscopic properties of a norfloxacin-single stranded DNA complex with those of norfloxacin-double stranded DNA complex. Norfloxacin binds to both double-and single stranded DNA, and we observed the following spectroscopic changes for both complexes: hypochromism in the norfloxacin absorption region in the absorption spectrum, the characteristic induced CD spectrum consisting of a weak positive band at 323 nm and a strong positive band at 280-300 nm followed by a negative band in the 260 nm region, a strong decrease in the fluorescence intensity and a red-shift in the fluorescence emission spectrum, and shorter fluorescence decay times. These results indicate that the environments of the bound norfloxacin in both DNAs are similar, although the equilibrium constant of the norfloxacin-single stranded DNA was twice as high as the norfloxacin-double stranded DNA complex. Both complexes were thermodynamically favored with similar negative Δ$G^o$. Negative Δ$H^o$ terms contribute to these spontaneous reactions; Δ$S^o$ term was unfavorable.

• 약학회지
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• 제36권6호
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• pp.577-581
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• 1992

Norfloxacin complexes of $Fe^{2+}$, $Cu^{2+}$ and $Al^{3+}$ have been prepared as solids. The stoichiometry of the complexes has been established. IR investigation indicates the metal-ligating sites in norfloxacin. The bioactivities of complexes all lower than that of norfloxacin. The solubilities and partition coefficients have been measured as a function of temperature. The data are used to evaluate the thermodynamic parameters ${\Delta}G$, ${\Delta}H$, ${\Delta}S$ for the solute transfer process and compared with the parent quinolone, norfloxacin. The existence of such complexes is discussed in the light of quinolone mode-of-action theories.

• Biomolecules & Therapeutics
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• 제7권2호
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• pp.164-169
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• 1999

The synthesis and antimicrobial activity of N-substituted glycol derivatives of Norfloxacin were described. Norfloxacin was treated with chloroacetyl chloride to yield chloroacetyl norfloxacin (1). This compounds was reacted with alkyldiamines to afford bivalent ligand quinolone carboxylic acids (2-6), which was added to pivaloyloxymethyl chloride to give bivalent ligand pivaloyloxymethyl quinolone carboxylates (7-11). Chloroacetyl norfloxacin (1) treated with alkylamines to obtain monovalent ligand quinolone carboxylic acids (12-15), which was reacted with pivaloyloxymethyl chloride to get monovalent ligand pivaloyloxymethyl quinolone carboxylates (16-19). Free carboxylic quinolones (2-6, 12-15) showed little stronger activities to their pivaloyloxymethyl esters (7-11, 16-19). In monovalent ligand quinolone analogues, longer a1kyl chain com-pounds showed stronger activities than shorter one.

• 대한수의학회지
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• 제39권2호
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• pp.365-369
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• 1999

A study on quinolone antibacterial, norfloxacin, was performed to apply for the control of bacterial diseases in eel (Anguilla japonica). Norfloxacin was proved excellent in antibacterial activity and sensitivity against fish bacterial pathogens when compared with the existing antibacterials and antibiotics. And any side effect was not observed during the period of indicated use. An outline of minimal inhibitory concentration was $0.03{\sim}0.1{\mu}g/ml$, $TLm_{48h}$ value was 3,500mg/l. The residual time of the day in fish body was less than 17 days and any pathological changes were not observed. The study has revealed that norfloxacin can be applied to treat some fish bacterial disease by the dosage of 100g/day/ton of fish body weight for about 3 days perorally. Further, norfloxacin may be used for the control of bacterial pathogens in eel.

• Journal of Microbiology and Biotechnology
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• 제23권9호
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• pp.1293-1303
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• 2013

Antibiotic resistance of soilborne Acinetobacter species has been poorly explored. In this study, norfloxacin resistance of a soil bacterium, Acinetobacter oleivorans DR1, was investigated. The frequencies of mutant appearance of all tested non-pathogenic Acinetobacter strains were lower than those of pathogenic strains under minimum inhibitory concentration (MIC). When the quinolone-resistance-determining region of the gyrA gene was examined, only one mutant (His78Asn) out of 10 resistant variants had a mutation. Whole transcriptome analysis using a RNA-Seq demonstrated that genes involved in SOS response and DNA repair were significantly up-regulated by norfloxacin. Determining the MICs of survival cells after norfloxacin treatment confirmed some of those cells were indeed persister cells. Ten colonies, randomly selected from among those that survived in the presence of norfloxacin, did not exhibit increased MIC. Thus, both the low mutation frequency of the target gene and SOS response under norfloxacin suggested that persister formation might contribute to the resistance of DR1 against norfloxacin. The persister frequency increased without a change in MIC when stationary phase cells, low growth rates conditions, and growth-deficient dnaJ mutant were used. Taken together, our comprehensive approach, which included mutational analysis of the target gene, persister formation assays, and RNA sequencing, indicated that DR1 survival when exposed to norfloxacin is related not only to target gene mutation but also to persister formation, possibly through up-regulation of the SOS response and DNA repair genes.

• Archives of Pharmacal Research
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• 제19권5호
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• pp.353-358
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• 1996

E. coli 11 and E. coli 101, clinical isolates of Escherichia coli were resistant to various quinolones, especially MICs to norfloxacin of both strains were higher than 100 mg/ml. In the presence of carbonyl cyanide m-chlorophenylhydrazone, a proton gradient uncoupler, norfloxacin uptake in both strains was increased, suggesting that an efflux system play an important role in the norfloxacin resistance. Outer membrane proteins of the susceptible and resistant strains which could affect the route of norfloxacin entry into cells were different. When quinolone resistance determining region(QRDR) of gyrA was amplified using PCR and cut with Hinf I, QRDR in the susceptible strain yielded two fragments while QRDRs in E. coli 11 and E. coli 101 yielded only one uncut fragment. When DNA sequence of QRDR was analyzed, there were two mutations as Ser-83 and Asp-87 in both resistant strains. these residues were changed to Leu-83 and Asn-87, respectively. These results showed that the norfloxacin resistance of E. coli 11 and E. coli 101 was resulted from multiple changes-an altered DNA gyrase A subunit, a change in route of drug entry, and reduction in quinolone concentration inside cells due to an efflux system.