Disease relevance of (6R,7R)-7-[[(2E)-2-(2-aminothiazol-4-yl)-2-methoxyimino-acetyl]amino]-3-[(4-oxazol-5-yl-1-pyridyl)methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

• DQ-2556 also had high affinities for PBPs 1B and 1A of E. coli [1].
• Against Pseudomonas aeruginosa, DQ-2556 was slightly less active than ceftazidime [2].
• Haemophilus influenzae and Neisseria gonorrhoeae were also highly susceptible to DQ-2556 [2].
• The metabolic disposition of DQ-2556 was studied in rats, rabbits, dogs, and monkeys after an intravenous administration of 20 mg of 14C-labeled drug per kg of body weight [3].
• Against gram-negative bacteria, DQ-2556 showed almost the same activity as those shown by cefpirome and cefepime [1].

High impact information on (6R,7R)-7-[[(2E)-2-(2-aminothiazol-4-yl)-2-methoxyimino-acetyl]amino]-3-[(4-oxazol-5-yl-1-pyridyl)methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

• The results of a protein-binding study by ultracentrifugation indicated that DQ-2556 was 20 to 30% bound to serum proteins in animals and its affinity was low [3].
• When cells of E. coli were exposed to various concentrations of DQ-2556, filamentous cells were observed at concentrations of 0.0008 micrograms/ml and greater, spheroplasts started to form at 0.025 micrograms/ml, and subsequent cell lysis was observed [1].
• DQ-2556 had no effect on brush border transport systems for organic anions or dipeptides and basolateral transport systems for organic cations or anions in dogs, rabbits and rats [4].
• The MIC of DQ-2556 for Esch. coli increased four-fold in an OmpF-deficient mutant, indicating that the OmpF porin was one of the major routes for penetration of DQ-2556 into Esch. coli cells [5].
• In the rabbit, the pharmacokinetics of DQ-2556 was linear even up to a dose of 1200 mg/kg and no unusual pharmacokinetic behavior was observed [6].

Biological context of (6R,7R)-7-[[(2E)-2-(2-aminothiazol-4-yl)-2-methoxyimino-acetyl]amino]-3-[(4-oxazol-5-yl-1-pyridyl)methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

• It was also shown that the glomerular filtration rate (GFR) remained constant up to a dose of 1000 mg/kg of DQ-2556 in the rat, whereas the GFR decreased by 95.1% at a dose of 1200 mg/kg [6].
• In the examination of hemodynamics, DQ-2556 significantly decreased the blood flow with increased vascular resistance in the renal artery during and after a single injection [7].

Associations of (6R,7R)-7-[[(2E)-2-(2-aminothiazol-4-yl)-2-methoxyimino-acetyl]amino]-3-[(4-oxazol-5-yl-1-pyridyl)methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid with other chemical compounds

• Nonlinear pharmacokinetics of DQ-2556, a new 3-quaternary ammonium cephalosporin antibiotic, in rats caused by non-Michaelis-Menten type, dose-dependent renal clearance [6].
• The safety and pharmacokinetic properties of DQ-2556, a new parenteral cephalosporin, were evaluated using healthy volunteers after 5-minute intravenous infusion of doses of 250, 500, 1000, or 2000 mg and a 1-hour infusion of 2000 mg, and an intramuscular dose of 500 mg [8].

Analytical, diagnostic and therapeutic context of (6R,7R)-7-[[(2E)-2-(2-aminothiazol-4-yl)-2-methoxyimino-acetyl]amino]-3-[(4-oxazol-5-yl-1-pyridyl)methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

• These results suggest that DQ-2556 is worthy for subsequent clinical trials [1].
• A sensitive method for the determination of DQ-2556 by high-performance liquid chromatography was established [9].
• The renal clearance experiments demonstrated that DQ-2556 is excreted by glomerular filtration [6].

References