Evidence of different profiles of side effects and drug-drug interactions among the quinolones - The pharmacokinetic standpoint

Recent pharmacokinetic data, interaction profiles, and specific tolerance problems associated with the fluoroquinolones are reviewed. Oral absorption was highest for levofloxacin (99-100%), and 500 mg oral levofloxacin achieved a much higher initial concentration than either sparfloxacin (400 mg) or ciprofloxacin (500 mg, b.i.d.), with a slow drop in concentration over 24 h. The C-max achieved after an oral 250-mg dose ranged from a low of 1.2 mug/ml/70 kg for ciprofloxacin, to 1.71 for gatifloxacin and 2.17 for moxifloxacin, to a high of 2.48 for levofloxacin (p< 0.01). Ciprofloxacin had the lowest AUC of 4.6 <mu>g/ml/70 kg, gatifloxacin 15, levofloxacin 17.9, and moxifloxacin 19.7 mug/ml/70 kg (p < 0.01). All fluoroquinolones interact with multivalent cation-containing products and bioavailability is reduced by 50% when coadministered with iron compounds (ciprofloxacin and moxifloxacin are more affected than levofloxacin or gemifloxacin). The interaction between theophylline and fluoroquinolones is most marked with enoxacin, pefloxacin, and ciprofloxacin, with no such interaction reported for levofloxacin. Sparfloxacin is associated with cardiac manifestations of QTc prolongation and has a high phototoxicity potential. Moxifloxacin is currently under observation concerning QTc effects. Levofloxacin has no QTc: prolongation and a very low phototoxic potential, making it one of the safest new fluoroquinolones. Copyright (C) 2001 S. Karger AG, Basel.