The chemistry and biological profile of trovafloxacin.

The fluoroquinolone antibacterials are noted for their activity after oral administration and potent activity against Gram-negative pathogens. Trovafloxacin (CP-99,219) is a new quinolone antibacterial characterized by a novel 3-azabicyclo[3.1.0]hexyl substituent at the C-7 position, which was discovered in the course of a programme targeting improved activity compared with ciprofloxacin against Gram-positive aerobic organisms and anaerobes, as well as an extended elimination half-life. An overview of the chemical properties of trovafloxacin is given. Trovafloxacin exhibits excellent potency against Gram-positive organisms and anaerobes, while retaining the potent Gram-negative activity of ciprofloxacin. Its pharmacokinetic properties in humans have been shown to be compatible with a once-daily dosing regimen. The combined spectrum and pharmacokinetics of trovafloxacin have been demonstrated to result in excellent efficacy in both animal models of infections and human clinical trials. Phase II and Phase III programmes have been completed.