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 p roblems associated with the fluoroquinolones are reviewed. Oral absorption was highest for levofloxacin (99-100%), and 500 mg oral levofloxacin achiev ed 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 mu g/ml/70 kg for ciprofloxacin, to 1.71 for gatifloxacin and 2.17 for moxiflo xacin, 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 m oxifloxacin 19.7 mug/ml/70 kg (p < 0.01). All fluoroquinolones interact wit h 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 betw een theophylline and fluoroquinolones is most marked with enoxacin, pefloxa cin, 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 ob servation concerning QTc effects. Levofloxacin has no QTc: prolongation and a very low phototoxic potential, making it one of the safest new fluoroqui nolones. Copyright (C) 2001 S. Karger AG, Basel.