Disease relevance of (6R,7R)-7-[[(2R)-2-[(5-carboxy1H-imidazole-4-carbonyl)amino]-2-phenyl-acetyl]amino]-8-oxo-3-[[4-(2-sulfoethyl)-1-pyridyl]methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

• Results of the study demonstrate that cefpimizole offers no advantage over currently available antibiotics in the treatment of uncomplicated gonorrhea in men [1].
• Overall, cefpimizole exhibited limited activity against gram-positive cocci and members of the family Enterobacteriaceae as compared with the other cephalosporins tested [2].
• Further, bactericidal effects of AC-1370 against Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae were augmented when they were each cultured with mouse or human leukocytes [3].
• On a weight basis the in-vitro activity of cefpimizole against Neisseria gonorrhoeae was similar to that of APPG [4].
• Acute and subacute toxicity studies of AC-1370 sodium in mice and rats [5].

High impact information on (6R,7R)-7-[[(2R)-2-[(5-carboxy1H-imidazole-4-carbonyl)amino]-2-phenyl-acetyl]amino]-8-oxo-3-[[4-(2-sulfoethyl)-1-pyridyl]methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

• The median peak concentrations in plasma for the 500- and 1,000-mg twice-daily dosages of cefpimizole were, respectively, 21.6 and 45.5 micrograms/ml on day 1, 16.2 and 43.7 micrograms/ml on day 3, and 20.1 and 41.4 micrograms/ml on day 6 of the study [6].
• The kinetics of cefpimizole after intramuscular administration were similar to the kinetics obtained after intravenous infusion [7].
• Pharmacokinetics and dose proportionality of cefpimizole in normal humans after intramuscular administration [7].
• Most of the AC-1370-binding cells were macrophages, and few neutrophils bound AC-1370 [8].
• This activity of the culture supernatant of AC-1370-stimulated macrophages was abolished by digestion with trypsin but not by heat treatment at 56 degrees C for 30 min [8].

Chemical compound and disease context of (6R,7R)-7-[[(2R)-2-[(5-carboxy1H-imidazole-4-carbonyl)amino]-2-phenyl-acetyl]amino]-8-oxo-3-[[4-(2-sulfoethyl)-1-pyridyl]methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

• Thus, for acute uncomplicated gonorrhea cefpimizole is similar in efficacy to cefotaxime and APPG but has a higher frequency of pain at the injection site [4].
• One hundred sixteen patients (92 men and 24 women) with suspected uncomplicated gonorrhea were randomized in a double-blind manner to receive intramuscular treatment with 1.0 g of cefpimizole, 1.0 g of cefotaxime, or 4.8 x 10(6) units of aqueous procaine penicillin G (APPG) with 1 g of oral probenecid [4].

Biological context of (6R,7R)-7-[[(2R)-2-[(5-carboxy1H-imidazole-4-carbonyl)amino]-2-phenyl-acetyl]amino]-8-oxo-3-[[4-(2-sulfoethyl)-1-pyridyl]methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

• The results of the multiple-dose study indicated that no apparent change in the distribution or elimination kinetics of cefpimizole occurred after the administration of 1-, 2-, and 4-g doses for 7 days, three times a day [9].
• AC-1370 augmented phagocytosis by mouse macrophages in vitro and in vivo, by mouse neutrophils in vivo, and by human neutrophils in vitro [3].
• Random migration and chemotaxis of mouse and human neutrophils were increased by the addition of AC-1370 [3].

Anatomical context of (6R,7R)-7-[[(2R)-2-[(5-carboxy1H-imidazole-4-carbonyl)amino]-2-phenyl-acetyl]amino]-8-oxo-3-[[4-(2-sulfoethyl)-1-pyridyl]methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

• AC-1370 enhanced phagocytic functions of macrophages and neutrophils [8].
• Mechanism of action of AC-1370 on phagocyte functions [8].

Associations of (6R,7R)-7-[[(2R)-2-[(5-carboxy1H-imidazole-4-carbonyl)amino]-2-phenyl-acetyl]amino]-8-oxo-3-[[4-(2-sulfoethyl)-1-pyridyl]methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid with other chemical compounds

• Nitroblue tetrazolium reduction by human neutrophils was enhanced by the addition of AC-1370 [3].
• The effects of a new semisynthetic cephalosporin, AC-1370, on phagocyte functions were compared with those of cefoperazone [3].
• The efficacy of AC-1370 was more dependent on neutrophils than that of cefoperazone [10].

Gene context of (6R,7R)-7-[[(2R)-2-[(5-carboxy1H-imidazole-4-carbonyl)amino]-2-phenyl-acetyl]amino]-8-oxo-3-[[4-(2-sulfoethyl)-1-pyridyl]methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

• In vitro evaluation of U63196-E (AC-1370): antimicrobial activity, beta-lactamase stability, and beta-lactamase inhibition [11].

Analytical, diagnostic and therapeutic context of (6R,7R)-7-[[(2R)-2-[(5-carboxy1H-imidazole-4-carbonyl)amino]-2-phenyl-acetyl]amino]-8-oxo-3-[[4-(2-sulfoethyl)-1-pyridyl]methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

• Pharmacokinetics of cefpimizole in normal humans after single- and multiple-dose intravenous infusions [9].
• Tolerance and disposition of cefpimizole in normal human volunteers after intramuscular administration [6].

References