Comparative pharmacokinetics and pharmacodynamics of the newer fluoroquinolone antibacterials
Abstract
A number of new fluoroquinolone antibacterials have been released for clinical use in recent years. These new agents exhibit enhanced activity against Gram-positive organisms while retaining much of the Gram-negative activity of the earlier agents within the same class. The pharmacokinetics of most of these agents are well described including serum pharmacokinetics, tissue and fluid distribution, and pharmacokinetics in renal and hepatic disease. When compared with earlier agents within this class (i.e. ciprofloxacin), the newer agents retain the wide distribution characteristics; however, they exhibit a more prolonged elimination, which, in part, supports single daily administration for these agents. Based on their predominant renal elimination, dosage adjustment is necessary in the presence of renal disease for ciprofloxacin, levofloxacin, gatifloxacin and sitafloxacin. Drug interactions, particularly with multivalent cations (calcium/aluminium-containing antacids and iron products), remain a problem for the newer agents, resulting in reduced absorption requiring separate administration times to maximise bioavailability. However, the newer agents do not appear to interfere significantly with the cytochrome P450 system, thus minimising the potential for interactions with other drugs metabolised by this system. The pharmacodynamic properties of the fluoroquinolones have been well described. The bactericidal activity is maximised when the ratios of peak plasma drug…
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