Disease relevance of Fluorinated quinolone

• We used microarray analysis on isolated human hepatocytes to understand the mechanisms underlying the idiosyncratic toxicity induced by trovafloxacin [1].
• CONCLUSION: Based on the results presented here, trovafloxacin is a promising agent for single-dose therapy of uncomplicated gonorrhea [2].
• PATIENTS AND METHODS: In this multicenter, double-blind trial, 625 patients (270 men, 355 women) with uncomplicated gonococcal urethritis or cervicitis received one 100-mg tablet of trovafloxacin or two 200-mg capsules of ofloxacin as a single dose under direct supervision [2].
• PURPOSE: To compare trovafloxacin, a new quinolone antibiotic with enhanced activity against Neisseria gonorrhoeae, with ofloxacin as single-dose oral therapy for uncomplicated gonococcal urethritis or cervicitis [2].
• Fulminant toxic epidermal necrolysis induced by trovafloxacin [3].

Psychiatry related information on Fluorinated quinolone

• Using a device developed at our institute for the simultaneous registration of the activity of rats housed in single cages, we have investigated the effects of trovafloxacin, fleroxacin or ofloxacin on the locomotor activity of juvenile and adult rats (11 per group) after oral administration of 600 mg/kg for 5 consecutive days [4].

High impact information on Fluorinated quinolone

• Microarray analysis in human hepatocytes suggests a mechanism for hepatotoxicity induced by trovafloxacin [1].
• Randomized trial of trovafloxacin and ofloxacin for single-dose therapy of gonorrhea. Trovafloxacin Gonorrhea Study Group [2].
• Each treatment was well tolerated; vaginitis was the most frequently observed side effect (4% trovafloxacin, 7% ofloxacin) [2].
• Beginning 18 h after infection, the rats received once daily subcutaneous phosphate-buffered saline, levofloxacin, moxifloxacin, or trovafloxacin at 50 or 100 mg/kg of body weight [5].
• Based on the I(E)-log AUC/MIC relationships, breakpoints (BPs) that are equivalent to a CIP AUC/MIC ratio of 125 h were predicted for GRX, MXF, and TVA (75 to 78 h), GAT and GEM (95 to 103 h) and LVX (115 h) [6].

Chemical compound and disease context of Fluorinated quinolone

• Dosing regimens were chosen to obtain a comparable area under the concentration-time curve from 0 to infinity/MIC ratio of 27.9 min for trovafloxacin (75 mg/kg of body weight) and of 32.6 min for ciprofloxacin (12.5 mg/kg) [7].
• The antimicrobial activities of trovafloxacin, moxifloxacin, sanfetrinem, quinupristin-dalfopristin, and 14 other antimicrobial agents against 218 Bacteroides fragilis group strains were determined [8].
• Two hundred fifty isolates of Mycobacterium tuberculosis were evaluated for susceptibility to ciprofloxacin, ofloxacin, levofloxacin, grepafloxacin, trovafloxacin, and gemifloxacin (SB-265805) [9].
• Mycoplasma hominis was highly susceptible to trovafloxacin (MIC = 0.06 microgram/ml) and sparfloxacin (MIC = 0.03 microgram/ml) and less susceptible to ofloxacin (MIC = 0.5 microgram/ml) [10].
• The potency of trovafloxacin against susceptible organisms, coupled with its rapid penetration of CSF following the intravenous administration of alatrofloxacin, suggests that it may be useful in the treatment of bacterial meningitis in humans [11].

Biological context of Fluorinated quinolone

• Although the pharmacokinetics and concentrations of trovafloxacin in serum were similar between young and old mice, the levels in tissue were higher in senescent mice than in young mice [12].
• Although the rate of killing with ofloxacin was substantially slower than that with trovafloxacin, ofloxacin was also able to eradicate all eight strains from the model, despite a simulated area under the inhibitory curve/MIC ratio (AUC/MIC) of only 49 [13].
• The oral bioavailability of trovafloxacin was 68, 58, and 85% in rats, dogs, and monkeys, respectively [14].
• Anti-Toxoplasma gondii activities and structure-activity relationships of novel fluoroquinolones related to trovafloxacin [15].
• The 50% inhibitory concentration (IC50) of trovafloxacin against T. gondii was 2.93 microM; the IC50 of the 11 analogs ranged from 0.53 to 14 [15].

Anatomical context of Fluorinated quinolone

• Effect of trovafloxacin on production of cytokines by human monocytes [16].
• In our well-established rabbit model of meningitis, we conducted experiments to determine the concentrations of CP-99,219 in cerebrospinal fluid (CSF) after intravenous administration and its ability to eradicate two penicillin-resistant pneumococcal isolates [17].
• The aim of the study was to determine if immunomodulation of host defense with recombinant murine granulocyte colony-stimulating factor (G-CSF) improves the efficacy of trovafloxacin or moxifloxacin in abscesses containing Bacillus fragilis ATCC 23745 and different Escherichia coli strains varying in virulence [18].
• Trovafloxacin (0.25 micrograms/ml) reduced bacterial counts of two L. pneumophila strains grown in guinea pig alveolar macrophages by > 2 log10 CFU/ml, without regrowth, under drug-free conditions over a 3-day period; trovafloxacin was significantly more active than ofloxacin or erythromycin (0.25 to 1 microgram/ml) in this assay [19].
• The penetration of trovafloxacin into human polymorphonuclear leukocytes (PMNs), human peritoneal macrophages, and tissue-cultured epithelial cells (McCoy cells) was evaluated [20].

Associations of Fluorinated quinolone with other chemical compounds

• Ciprofloxacin, a fluorinated quinolone, is a powerful antibiotic widely used for its broad spectrum of activity in ambulatory and long-term care setting [21].
• Six strains of staphylococci were exposed to levofloxacin, moxifloxacin, or trovafloxacin in an in vitro pharmacodynamic model under both aerobic and anaerobic conditions [22].
• The pharmacokinetics of trovafloxacin when administered orally as the active form or intravenously as the prodrug (alatrofloxacin) are not altered in subjects with AIDS compared to those in healthy adults [23].
• Against the two streptococcal isolates, trovafloxacin significantly (P < 0.05) decreased bacterial counts in the vegetations but was less effective than the control drug, ceftriaxone [24].
• The five recently developed fluoroquinolones (gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin, and trovafloxacin) showed greater bioavailability, longer half-lives, and higher C(max)s than ciprofloxacin [25].

Gene context of Fluorinated quinolone

• Cloning and nucleotide sequence of the DNA gyrase (gyrA) gene from Mycoplasma hominis and characterization of quinolone-resistant mutants selected in vitro with trovafloxacin [26].
• The relevance of this in vitro observation was explored by examining TNF-alpha and IL-6 responses in trovafloxacin-treated mice [27].
• Twelve hours after initiation of therapy, however, TNF and IL-1beta were higher in trovafloxacin-treated animals (TNF, 61 U/mL versus 7 U/mL; P = 0.001; IL-1beta, 4320 pg/mL versus 427 pg/mL; P = 0.006) [28].
• In comparison with ceftriaxone, trovafloxacin resulted in lower tumour necrosis factor (TNF) and interleukin 1beta (IL-1beta) CSF levels 2 h after the initiation of treatment (TNF levels, median 26 U/mL versus 141 U/mL; P = 0.02; IL-1beta levels 455 pg/mL versus 1399 pg/mL; P = 0.02) [28].
• Whether the greater intrinsic activity of trovafloxacin might allow its use in treating MRSA and enterococcal infections remains to be seen [29].

Analytical, diagnostic and therapeutic context of Fluorinated quinolone

• Elevated international normalized ratio associated with trovafloxacin [30].
• Since reported data on ciprofloxacin, a fluorinated quinolone, are conflicting, we compared intravenous and oral administration in cystic fibrosis patients when treating them for mild symptoms of pulmonary infection [31].
• Compared with untreated (control) animals, three doses of CP-99,219 given 5 h apart significantly reduced the bacterial count in CSF by 5 to 6 log10 CFU at 10 h [17].
• The in vitro and in vivo antimicrobial activities of trovafloxacin and its pharmacokinetics in laboratory animals provide support for the ongoing and planned human phase II and III clinical trials [32].
• The antimicrobial activity of trovafloxacin for 557 strains of anaerobic bacteria was determined by the National Committee for Clinical Laboratory Standards-approved Wadsworth agar dilution technique [33].

References