Linezolid Pharmacia Corp.
Linezolid is an oxazolidinone developed by Pharmacia (formerly Pharmacia & Upjohn) for the treatment of multi-resistant Gram-positive infections [187765,317456]. It binds to ribosomal 50S subunits, most likely within domain V within the 23S rRNA peptidyl transferase and a secondary interaction with the 30S subunit. This results in inhibition of the initiation of protein translation at an early point, which is probably N-formylmethionyl-tRNA [335843]. No direct action on DNA or RNA synthesis has been observed [220169]. Linezolid resistance due to a 23S rRNA mutation may emerge in Enterococci during therapy with this antimicrobial, and may be associated with clinical failure [368652]. Following FDA approval, linezolid was launched in May 2000 [368526,368652]. In April 2000, the FDA approved linezolid injection, tablets and oral suspension for the treatment of patients with infections caused by Gram-positive bacteria. It is indicated for adults in the treatment of nosocomial pneumonia, community-acquired pneumonia (CAP), complicated and uncomplicated skin and skin structure infections and vancomycin-resistant enterococcus (VRE) infections caused by methicillin-resistant Staphylococcus aureus (MRSA), VRE faecium and penicillin-susceptible Streptococcus pneumoniae [363503]. The FDA, however, did not grant Pharmacia indications for linezolid in the treatment of CAP due to either penicillin-resistant S aureus (PRSA) or MRSA. In May 2000, Merrill Lynch predicted sales for 2000 to be US $50 million, rising to US $760 million in 2004 [366910]. In February 2000, P&U predicted that peak sales of the drug had the potential to reach in excess of US $750 million [358429]. In February 1999, Morgan Stanley Dean Witter predicted sales of US $40 million in 2000 rising to US $275 million in 2005 [319855]. In December 1998, Deutsche Bank predicted sales of US $100 million in 2000 rising to US $300 million in 2002 [316769].
Pharmaceutical Research and Development Division, Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT 06492, USA. john.barrett@bms.com
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D000081:Acetamides / Q000009:adverse effects / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D001419:Bacteria / Q000187:drug effects; D001424:Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D000075202:Contraindications; D006801:Humans; D000069349:Linezolid; D023303:Oxazolidinones / Q000009:adverse effects / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D013329:Structure-Activity Relationship
D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D000069349:Linezolid