• Toxicological Research
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• v.26 no.1
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• pp.9-14
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• 2010

The evaluation of eye and skin irritation potential is essential to ensuring the safety of human in contact with a wide variety of substances. Despite this importance of irritation test, little is known with respect to the irritation potency of lomefloxacin, a fluoroquinolone antibiotic, which has been known to cause phototoxicity with an abnormal reaction of the skin. Thus, to investigate the tendency of lomefloxacin to cause eye and skin irritation, we carried out in vitro eye irritation test using Balb/c 3T3, and in vitro skin irritation test using $KeraSkin^{TM}$ human skin model system. 3T3 neutral red uptake assay has been proposed as a potential replacement alternative for the Draize Eye irritation test. In this study, the $IC_{50}$ value obtained for lomefloxacin was 375 ${\mu}g$. According to the classification model used for determining in vitro categories, lomefloxacin was classified as moderately irritant. For evaluation of skin irritation, engineered epidermal equivalents ($KeraSkin^{TM}$) were subjected to 10 and 25 mg of lomefloxacin for 15 minutes. Tissue damage was assessed by tissue viability evaluation, and by the release of a pro-inflammatory mediator, interleukin- 1${\alpha}$. Lomefloxacin increased the interleukin-1${\alpha}$ release after 15 minutes of exposure and 42 hours of post incubation, although no decrease in viability was observed. Therefore, lomefloxacin is considered to be moderately irritant to skin and eye.

• Korean Journal of Clinical Pharmacy
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• v.7 no.2
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• pp.67-72
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• 1997

The bioequivalence of two lomefloxacin tablets was evaluated in 16 normal male volunteers (age $21\sim30$ yrs) following oral administration. Test product was 'Lomaxacin tablet' made by Kolon Pharmaceutical Co. and reference product was 'Maxaquin tablet' made by Searle Ciba-Geigy Korea Co. After one tablet containing 400 mg of lomefloxacin was administered, blood was taken at predetermined time intervals and the concentration of the drug in plasma was determined with an HPLC method using fluorescence detector. AUC, $C_{max},\;and\;T_{max}$ were calculated and statistically analyzed for the bioequivalence of the two products. The results showed that the differences in AUC, $C_{max},\;and\;T_{max}$ between two products were $0.90\%,\;1.09\%,\;and\;2.44\%$, respectively. The powers (1-${\beta}$) for AUC, $C_{max},\;and\;T_{max}\;were\;>95\%,\;>95\%,\;and\;93.8\%$, respectively Detectable differences $(\Delta)$ and confidence intervals were all less than $20\%$. All of these parameters met the criteria of KFDA for bioequivalence, indicating that 'Lomaxacin tablet' is bioequivalent to 'Maxaquin tablet'.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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• pp.12-12
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• 1997

CFC-222 is a novel fluoroqinolone antibacterial agent synthesized and under development by the Cheil Jedang Corporation, Korea. CFC-222 exerts the antibacterial activity by inhibition of bacterial DNA gyrase leading to bactericidal action. In in vitro and in vivo preclinical testing, CFC-222 has been shown to possess a broad spectrum of antibacterial activity. In particular CFC-222 is very potent against Gram-positive bacteria such as Staphylococcus spp., Streptocuccus spp. (in particular penicillin G-resistant and -susceptible S. pneumoniae) and Enterococcus spp. when compared to other quinolones (ciprofloxacin, ofloxacin or lomefloxacin). CFC-222 also showed potent activity against the methicillin resistant clinical isolates of S. aureus (MRSA). Against Gram-negative bacteria (E. coli, Pseudomonas and Sarcina) the activity of CFC-222 was slightly weaker than that of ciprofloxacin, but was more potent than that of ofloxacin or lomefloxacin. In urinary systemic infections caused by both Gram-positive and -negative bacteria, CFC-222 demonstrated a potent therapeutic efficacy in particular against Cram-positive bacteria S. aureus, S. pyrogen 203 and S. pneumonia TypeIII.

• Toxicological Research
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• v.22 no.4
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• pp.423-429
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• 2006

Recent reports on the photocarcinogenicity and photogerotoxicity of many compounds led to an increasing awareness for the need of a standard approach to test for photogenotoxicity. The comet assay has been recently validated as a sensitive and specific test system for the quantification of DNA damage. Thus, the objectives of this study are to investigate the utility of photo-comet assay for detecting photo-mutagens, and to evaluate its ability to predict rodent photo-carcinogenicity. Photo-comet assays were performed using L5178Y $Tk^{+/-}$ mouse lymphoma cells on five test substances (8-methoxypsoralen, chlorpromazine, lomefloxacin, anthracene and retinoic acid) that demonstrated positive results in photocarcinogenicity tests. For the best discrimination between the test substance-mediated DNA damage and the undesirable DNA damage caused by direct UV absorption, a UV dose-response of the cells in the absence of the test substances was firstly fnalized. Out of 5 test substances, positive comet results were obtained for chlorpromazine, lomefloxacin, anthracene and retinoic acid while 8-methoxypsoralen found negative. An investigation into the predictive value of this photo-comet assay for determining the photocarcinogenicity showed that photo-comet assay has relatively high sensitivity. Therefore, the photo-comet assay with mammalian cells seems to be a good and sensitive predictor of the photocarcinogenic potential of new substances.

• Genomics & Informatics
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• v.16 no.3
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• pp.44-51
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• 2018

Fluoroquinolone (FQ) antibiotics are an important class of synthetic antibacterial agents. These are the most extensively used drugs for treating bacterial infections in the field of both human and veterinary medicine. Herein, the antibacterial and pharmacological properties of four fluoroquinolones: lomefloxacin, norfloxacin, ciprofloxacin, and ofloxacin have been studied. The objective of this study was to analyze the antibacterial characteristics of the different fluoroquinolones. Also, the pharmacological properties of the compounds including the Lipinski rule of five, absorption, distribution, metabolism, and excretion, LD50, drug likeliness, and toxicity were evaluated. We found that among all four FQ molecules, ofloxacin showed the highest antibacterial activity through in silico assays with a strong interaction (-38.52 kJ/mol) with the antibacterial target protein (topoisomerase-II DNA gyrase enzyme). The pharmacological and pharmacokinetic analysis also showed that the compounds ciprofloxacin, ofloxacin, lomefloxacin and norfloxacin have good pharmacological properties. Notably, ofloxacin was found to possess an IGC50 (concentration needed to inhibit 50% growth) value of $0.286{\mu}g/L$ against the Tetrahymena pyriformis protozoa. It also tested negative for the Ames toxicity test, showing its non-carcinogenic character.

• YAKHAK HOEJI
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• v.55 no.1
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• pp.22-31
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• 2011

This systematic review was conducted to assess the clinical effect of ocular fluoroquinolones used for the treatment of bacterial conjunctivitis. A literature search for randomized controlled clinical trials registered up to January 2010 based on PubMed database, using the following search terms: conjunctivitis and fluoroquinolones (besifloxacin, moxifloxacin, gatifloxacin, levofloxacin, lomefloxacin, ciprofloxacin and ofloxacin) were performed. Pooled data on the clinical resolution and bacterial eradication rates derived from selected 16 studies were reported as the relative risk (RR) and 95% confidence interval (95% CI) compared with placebo. Early clinical resolution and microbiological eradication rates in placebo were 28% and 62% respectively. Fluoroquinolones were significantly effective comparing to placebo: early RR 1.94 (95% CI 1.60~2.34) and late RR 1.30 (1.19~1.43) in clinical resolution rates, and early RR 1.75 (1.58~1.94) and late RR 1.28 (1.18~1.39) in microbiological eradication rates. Besifloxacin, ciprofloaxain and moxifloxacin in clinical resolution, and besifloxacin and levofloxacin in microbiological eradication showed higher RRs than pooled overall fluoroquinolones' RRs. New quinolones had higher antibacterial potencies for all pathogens isolated from bacterial conjunctivitis and resistant isolates than old generation quinolones. In conclusion, ocular 7 fluoroquinolones were all effective than placebo for bacterial conjunctivitis and there were differences between quinolones in early and late clinical resolutions and microbiological eradications, and no differences in safety comparing to placebo.

• Archives of Pharmacal Research
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• v.19 no.1
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• pp.52-59
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• 1996

The in vitro activity of LB20304 was evaluated against clinical isolates and compared with those of Q-35, ciprofloxacin, sparfloxacin, lomefloxacin and ofloxacin. LB20304 demonstrated 16-to 64-fold more potent activity than ciprofloxacin against gram-positive bacteria. LB20304 inhibited 90% of the isolates of methicillin-susceptible Staphylococcus aureus(MSSA) at a concentration of $0.016\mug/ml\; (MIC_{90}). MIC_{90}$ values of LB20304 against methicillin-resistant Staphylococcus aureus (MRSA), methicillin-susceptible Staphylococcus epidermidis (MSSE), methicillin-resistant S. epidermidis (MRSE) and Streptococcus pneumoniae were $2\mug/ml,\; 0.016\mug/ml,\; 0.5\mug/ml \;and\; 0.031\mug/ml,$ respectively. LB20304 was also very active against gram-negative bacteria. Against Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, Pseudomonas aeruginosa and Acinetobacter calcoaceticus, $MIC_{90}s of\; LB20304 were\; 0.031\mug/ml,\; 0.25\mug/ml,\; 2\mug/ml,\; 8\mug/ml\; and\; 0.5\mug/ml$, respectively. Its activity was comparable to that of ciprofloxacin but much better than those of Q-35, sparfloxacin, ofloxacin and lomefloxacin. LB20304 also exhibited the most potent acitvity among quinolones tested against laboratory standard strains, ofloxacin-resistant strains, .betha.-lactamase-producing strains and anaerobic strains. The inhibitory effect$ (IC_{50)$ of LB20304 on DNA gyrase from Micrococcus luteus, determined by the supercoiling assay, was 8-fold more potent than that of ciprofloxacin. LB20304 did not induce topoisomerase-associated DNA cleavage even at a concentration of 10 mg/ml, although ciprofloxacin induced DNA cleavage at a concentration of 1 mg/ml.

• Journal of fish pathology
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• v.9 no.2
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• pp.185-193
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• 1996

Extensive acquirement of drug resistance to traditional antibacterial agents poses a serious problem to eel aquaculturists. To collect the basic information for new drug development in the future, we assessed the in vitro antibacterial efficacy of 14 new quinolones with 75 isolates of Edwardsiella tarda from local aquaculture tanks of Anguilla japonica. Of all tested quinolones under development or marketed for human use, DU-6859 was most potent with its $MIC_{50}$ value of $0.05{\mu}g$/ml in broth microdilution assay. The drugs whose $MIC_{50}$ values ranged from 0.2 to $0.78{\mu}g$/ml were T-3762, Bay-y3118, ciprofloxacin, norfloxacin, ofloxcin and tosufloxacin. The weakest group of drugs, with their $MIC_{50}$ being 1.56-$3.13{\mu}g$/ml, were difloxacin, sparfloxacin, fleroxacin, Q-35, amifloxacin, lomefloxacin and enoxacin. The number of resistant strains, when arbitrarily defined with their MICs of $\geq6.25{\mu}g$/ml, was : 3 to T-3762, 3 to Bay-y3118, 44 to difloxacin, 16 to sparfloxacin, 13 to ciprofloxacin, 19 to fleroxacin, 36 to Q-35). 31 to amifloxacin, 5 to norfloxacin, 13 to ofloxacin, 31 to lomefloxacin, 41 to enoxacin, 12 to tosufloxacin and 0% to DU-6859, respectively. This information can be taken into consideration for the future development of fisheries antibacterial quinolones.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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• pp.57-63
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• 1997

Animal and clinical investigations have shown that fluoroquinolones, new quinolone antibacterial agents (NQs), are well absorbed across the intestinal tract, with a bioavailability of 60-90% after oral administration. Although some types of carrier-mediated intestinal transport mechanisms have been reported for enoxacin (ENX), ofloxacin (OFLX) and sparfloxacin (SPFX), recent results using a human intestinal epithelial cell line, Caco-2, indicated a passive or nonsaturable transport of SPFX, one of the most hydrophobic NQs. The mechanism underlying the intestinal absorption of NQs is still largely unknown. The distribution of NQs into peripheral tissues including erythrocytes is very rapid and their tissue-to-plasma concentration ratios (Kp) are considerably larger than those of inulin (an extracellular fluid space marker), in spite of almost complete ionization of NQs at the physiological pH. Our findings suggest that OFLX and lomefloxacin (LFLX) are taken up by rat erythrocytes via a transport system common to that of a water-soluble vitamin, nicotinic acid.

• Korean Journal of Veterinary Pathology
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• v.1 no.1
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• pp.40-45
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• 1997

The phototoxic potentials of LB20304a a new quinolone compound being developed by LG Chemical Ltd, and reference compounds (Ciprofloxacin; CPFX, Enoxacin; ENX and Lomefloxacin; LFLX) were compared in a murine model. in addition photostability of these compunds was studied after irradiation with long-wave UV light(UVA, 0, 0.3 1 or 3 Joule/$Cm^2$) When hairless mice(9 to 11 weeks old 19-26g) were orally administered with different dose levels of test compunds and exposed to UVA(40J/$cm^2$) inflammatory reactions were observed in a dose dependent manner. Among the compounds tested, LB20304a demonstrated the least phototoxic effects and showed no inflammatroy lesions at a dose level of 100mg.kg (Low dose). ENX and LFLX demonstrated much greater phototoxic reactions while CPFX showed similar or slightly greater phototoxic reactions compared to LB20304a. Similar to the in-vivo results the solutions of LB20304a and CPFX irradiated with UVA demonstrated reduced spectral changes compared to those of ENX and LFLX. In conclusion these data suggest that phototoxic potencies of the quinolones tested were; LFLX > ENX > CPFX $\geq$ LB20304a. No phototoxic dose of LB20304a in mice was 100 mg/kg.