In vitro antimalarial activity of trovafloxacin, a fourth-generation fluoroquinolone

Trovafloxacin, a recently-developed fourth-generation fluoroquinolone, is m ore potent than other quinolone drugs against a wide range of organisms inc luding Toxoplasma gondii. We assessed the in vitro antimalarial activity of trovafloxacin against three laboratory-adapted Plasmodium falciparum isola tes and compared the results with those of ciprofloxacin and norfloxacin. S ynchronous and asynchronous cultures were exposed to a range of drug concen trations, and growth inhibition was assessed using H-3-hypoxanthine incorpo ration. All isolates, both synchronous and asynchronous, exhibited comparab le sensitivities with trovafloxacin (EC50 range, 1.8 x 10(-5) to 3.7 x 10(- 5) mol/l) and ciprofloxacin (2.0 x 10(-5) to 3.9 x 10(-5) mol/l), but were less sensitive to norfloxacin (5.4 x 10(-5) to 6.6 x 10(-4) mol/l). These r esults confirm that ciprofloxacin is twice as potent as norfloxacin against P. falciparum in vitro, but also show that trovafloxacin and ciprofloxacin have similar antimalarial potency. The EC50 concentrations of all three dr ugs were generally higher than those achieved after conventional doses in h umans, suggesting that their clinical application may be limited to combina tion therapy. Recent reports of hepatotoxicity with trovafloxacin may also prevent the use of this drug in humans. However, newer fourth-generation qu inolones may prove safer and have similar antimalarial potency. (C) 2000 El sevier Science B.V. All rights reserved.