Ofloxacin and Levofloxacin (Tarivid/Cravit): Best-in-Class Antimicrobial Agents

Both ofloxacin (Tarivid), a second-generation fluoroquinolone, and levofloxacin (Cravit), a third-generation fluoroquinolone, were developed by Daiichi Pharmaceutical. Both are excellent antimicrobials with wide antibacterial spectrums, and levofloxacin is the world’s first optically active fluoroquinolone. Daiichi Pharmaceutical conducted research and development (R&D) over approximately 20 years to discover and develop these two drugs. The R&D process for ofloxacin was based on the notion that the physical properties of drugs affect not only blood levels but also metabolic and water-soluble pharmacokinetics, which determine overall efficacy. The project was initially implemented as unauthorized research, suggesting that researchers’ individual initiatives are important to pursue diverse ideas for innovation. Levofloxacin’s R&D process involved the difficult task of optical resolution of ofloxacin and resulted in two-times the antibacterial activity and a drastic reduction in side effects. Nevertheless, Daiichi Pharmaceutical was just 2 days ahead of its competitor in filing the patent application for levofloxacin, demonstrating the importance of time-based competition in the discovery of drugs with known mechanisms of action. A new asymmetric synthesis method was introduced for the mass production of levofloxacin. This enabled Daiichi Pharmaceutical to achieve its original goal of reducing the production costs of levofloxacin to no more than twice that of ofloxacin.