• Biomolecules & Therapeutics
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• v.4 no.2
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• pp.184-189
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• 1996

General pharmacological studies of LB20304a (a mesylate salt form of a new quinolone antibiotic LB20304 following oral administration of 300 mg/kg and 1000 mg/kg, almost maximum tolerance dose in mice and rat, respectively, were performed in terms of effects on general behaviour, central nervous system, gastrointestinal system, and blood coagulation system in mice and rats. With regards to general behaviour of mice, at oral dose of 300 mg/kg, LB20304a reduced muscle tone and locomotor activity. In terms of CNS, at oral treatment of 300 mg/kg, LB20304a showed some analgesic effects in mice, and oral dose of 1000 mg/kg caused drop in normal body temperature of rat, while it enhanced the pentylenetetrazole-induced clonic convulsion to tonic convulsion and/or death in mice at the doses of unto 300 mg/kg. In addition, LB20304a increased hexobarbital-induced sleeping time two and three times in mice at oral doses of 20 mg/kg and 300 mg/kg, respectively. Rota-rod and traction test in mice were not influenced by the dose of 300 mg/kg and 200 mg/kg, respectively. LB20304a reduced gastric secretion of rat at dose of 1000 mg/kg, and increased intestinal motility of mice at dose of 300 mg/kg. In rats, blood coagulation index, such as PT (prothrombin time) and aPTT (activated partial thromboplastin time) were not affected by the treatment of upto 1000 mg/kg of LB 20304a.

• 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.

• YAKHAK HOEJI
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• v.40 no.4
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• pp.438-441
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• 1996

The therapeutic activity of LB20304a was examined on experimental respiratory tract infection (RTI) caused by Klebsiella pneumoniae DT-S in mice. A single oral dose of LB 20304a (1.2mg/mouse) showed a rapid bacteriocidal activity in lung tissue at 4,7 and 24h after administration of drug. The in vivo activity of LB20304a was comparable to that of ciprofloxacin against K. pneumoniae infection, although in vitro MIC of LB20304a was four-fold higher than that of ciprofloxacin.

• 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.

• Biomolecules & Therapeutics
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• v.4 no.4
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• pp.378-384
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• 1996

In vitro activities of LB20304a were compared with those of grepafloxacin (OPC-17116), Q-35, ciprofloxacin, and sparfloxacin against 380 clinical isolates collected from general hospitals in 1996. LB 20304a was the most active agent against gram-positive strains including staphylococci, streptococci and enterococci. LB20304a was also very active against gram-negative bacteria and its activity was comparable to that of ciprofloxacin but better than those of grepafloxacin, Q-35 and sparfloxacin. The therapeutic effect of LB20304a was superior to those of sparfloxacin and ciprofloxacin against systemic infection by methicillin-resistant Staphylococcus aureus K283 (MRSA) in neutropenic mice. Against urinary tract infection induced by Escherichia coli 851E in mice, LB20304a was more active than sparfloxacin and ciprofloxacin. However, LB 20304a was slightly less active than that of ciprofloxacin against urinary tract infection by Pseudomonas aeruginosa 1912E, but better than that of sparfloxacin.

• YAKHAK HOEJI
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• v.40 no.3
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• pp.347-350
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• 1996

The post-antibiotic effect (PAE), which is defined as the period of time lag that the target organisms resume normal growth rate after complete removal of the antibiotics, of LB 20304 and ciprofloxacin was evaluated against Staphylococcus aureus 6538p and Escherichia coli 3190Y, respectively. The PAE was estimated by adding each antibiotic to a log phase of growth and incubating at $37^{\circ}$C for 1 h.Antibiotic was removed by centrifugation, and total viable cell counts were determined hourly for a further 10 h. The PAEs of LB20304 against S. aureus at concentrations of $1{\times}MIC\;and\;2{\mu}g/ml$ were 10 min and 93min, respectively. LB20304 showed a comparable PAE to ciprofloxacin. Against E. coli, the PAE of LB20304 was also similar to that of ciprofloxacin at concentration of $4{\times}MIC$ but it was much longer than that of ciprofloxacin at concentration of 2${\mu}g/ml$. LB20304 showed higher lethality than ciprofloxacin against both S. aureus and E. coli strains.

• Archives of Pharmacal Research
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• v.19 no.2
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• pp.143-147
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• 1996

LB20304 is a novel fluoroquinolone that exhibits a potent broad spectrum antibacterial activity against both gram-positve and gram-negative bacteria. The MICs (Minimal Inhibitory Concentration) of LB20304 were determined against both gram-positve and gram-negative bacteria under various conditions including several media, pHs, and inoculum concentrations. The in vitro activity of LB20304 was not significantly affected by the changes in testing conditions such as components of media and inoculum concentrations, but it was slightly reduced by acid condition. The MICs and MBCs (Minimal Bactericidal Concentration) of LB20304 against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa were hardly affected by the presence of 50 % human serum, mouse serum, guinea pig serum or horse serum, and the MBCs were equal to or at most four-times higher than the MiCs. The activities of LB20304 were decreased by the presence of high concentraion of $Mg^{++}$ or human urine (pH, 5.5) in the test media. The frequencies of mutants resistant to LB20304 were similar to or lower than those found in ciprofloxacin and sparfloxacin.

• Biomolecules & Therapeutics
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• v.3 no.4
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• pp.322-326
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• 1995

General pharmacology of LB20304, a quinolone antibiotic, were examined in terms of general behaviour, cardiovascular, and central nervous system. LB20304 at oral dose of 2,000 mg/kg did not induce significant behavioural changes in mice. In contrast with ciprofloxacin, LB20304 at dose of 20 mg/kg, iv. did not show any observable effects on the blood pressure in rats. Displacement of [$^3$H]muscimol binding to the rat brain synaptic membranes was measured. LB20304 was shown to be about five times less potent than ciprofloxacin in specific GABA receptor binding. Drug interaction between LB20304 and 4-biphenyl acetic acid, an active metabolite of fenbufen, was assessed in mice by measuring convulsion and/or subsequent death. A single oral pretreatment with 4-BPA at 400 mg/kg increased the incidence of convulsion and death after oral administration of ciprofloxacin at the doses of 25, 50, and 100 from zero of five to three of five, two of five, and four of five, respectively, whereas LB20304 alone or combination with 4-BPA caused neither convulsions nor death at the doses of 12.5, 25, 50, and 100 mg/kg, respectively. Quinolones-induced epileptogenic activities were assessed by a direct intracerebral injection of test articles. The CD$_{50}$ values (nmole) are as follows; 169.47, 35.36, 105.29, and 88.67 for LB20304, ciprofloxacin, of loxacin, and lomefloxacin, respectively. From these data, LB 20304 at therapeutic doses seems to be much more safe than any other quinolones tested.d.

• Archives of Pharmacal Research
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• v.19 no.5
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• pp.400-405
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• 1996

In vitro studies were conducted to dertermine the frequency rate of spontaneous resistance to LB20304 and to dertermine whether cross-resistance to other antimicrobial agents develops. In eight strains of bacteria, the frequency of mutation to LB20304 at the concentrations of four and eight times the minimal inhibitory concentration(MIC) ranaged from less than 4.0 ${\times}$ $10^{-10}$ to 2.2 $\{times}$ $10^{-10}$ . These results were similar to those founf for other new fluoroquinolones. THe development of stepwise resistance was determined by repeated subculture in broth in the presence of increasing concentration of the compounds. Exposure of bacteria to increasing concentrations of LB20304 resulted in the selection of organisms with higher MICs. There were 4- to 128-fold increases in the MIC of LB20304 for bacterial strains of Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli and Pseudomonas aeruginosa. However, those strains selected after repeated exposure were well within the susceptibility range for LB20304 except for Pseudomonas aeruginosa. The resistant isolates selected with LB20304 showed cross-resistance when tested against ciprofloxacin and vice versa.

• Archives of Pharmacal Research
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• v.19 no.4
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• pp.317-320
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• 1996

The time-kill curves of LB20304, a novel fluoroquinolone that has potent antibacterial activity against gram-positve and gram-negative bacteria, were calculated at the concentrations of 1/4-, 1/2-, 1-, 2- and 4-times the MIC against Staphylococcus aureus 77, Escherichia coli 3739E, Pseudomonas aeruginosa 1912E. The bactericidal activity of LB20304 for these strains was very rapid and comparable to that of ciprofloxacin. LB20304 produced a decrease in the $log_10$ CFU per milliliter of${\geq}$3 within 2 h at 4-times the MIC for all strains and consitently prevented regrowth of bacteria after 24 h of incubation. The MBCs (Minimal Bactericidal Concentration) of LB20304 against test organisms were equal to or at most four-times higher than the MICs.