ISHIKAWA T, MATSUNAGA N, TAWADA H, KURODA N, NAKAYAMA Y, IKEDA Y, TAGAWA Y, IIZAWA Y, OKONOGI K, HASHIGUCHI S, MIYAKE A; Interscience Conference on Antimicrobial Agents and Chemotherapy (42nd : 2002 : San Diego, Calif.).

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2002 Sep 27-30; 42: abstract no. F-332.

Takeda Chemical Industries, Ltd., Osaka, Japan

BACKGROUND: TAK-599 is a novel N-phosphono type prodrug of cephalosporin derivative T-91825, which was selected in our program as a potential anti-methicillin-resistant Staphylococcus aureus (MRSA) agent. RESULTS: Based on the high affinity for PBP2' (IC[50]; 0.90 microg/mL), T-91825 showed potent in vitro anti-MRSA activity (MIC against MRSA N133; 1 microg/mL) comparable to those of current anti-MRSA agents (vancomycin; 1 microg/mL, teicoplanin; 1 microg/mL, linezolid; 2 microg/mL). Unlike vancomycin and linezolid, T-91825 exhibited broad antibacterial spectrum including gram-negative bacteria. As T-91825 has insufficient water-solubility (2 mg/mL) for parenteral administration, a N-phosphono prodrug strategy was applied. TAK-599 is a crystalline form containing acetic acid solvate, and showed good stability in the solid state. In addition, in the presence of base such as sodium carbonate, TAK-599 dissolved in sterile water at a high concentration (>100 mg/mL) to give the stable parenteral fluid. In pharmacokinetic studies, when TAK-599 was administered intravenously to rats and monkeys, it was converted rapidly into T-91825 in blood. [figure: see text] CONCLUSIONS: These results show that TAK-599 is a highly promising parenteral cephalosporin targeted for MRSA.

Publication Types:

• Meeting Abstracts

Keywords:

• (E)-4-(4-((5-methyl-2-phenyl-1,3-oxazol-4-yl)methoxy)benzyloxyimino)-4-phenylbutyric acid
• Animals
• Anti-Bacterial Agents
• Antibodies
• Butyric Acids
• Cephalosporins
• Gram-Negative Bacteria
• In Vitro
• Microbial Sensitivity Tests
• Oxazoles
• Prodrugs
• Rats
• Staphylococcal Infections
• Staphylococcus aureus
• Thomsen-Friedenreich antibodies
• Vancomycin
• pharmacology

Other ID:

• GWAIDS0028201

UI: 102267825

From Meeting Abstracts