Absence of an effect of levofloxacin on warfarin pharmacokinetics and anticoagulation in male volunteers.

Some fluoroquinolone drug-drug interactions involving inhibition of the hepatic metabolism of agents such as theophylline and caffeine have been identified. This study was designed to investigate the potential interaction of the fluoroquinolone levofloxacin in a standard multiple-dose regimen with the oral anticoagulant warfarin. Sixteen healthy male volunteers were given a single oral dose of 30 mg warfarin sodium during a multiple-dose regimen of placebo or levofloxacin 500 mg twice daily, in a placebo-controlled, randomized, double-blind, two-way crossover design. Plasma R(+) and S(-) warfarin concentrations and prothrombin times were measured for 6 days after administration of each warfarin dose. The pharmacokinetic parameters of both enantiomers of warfarin were comparable in the absence and presence of levofloxacin, with no significant differences noted in warfarin peak plasma concentration, time to peak plasma concentration, apparent total body clearance, and terminal disposition half-life. Levofloxacin also had no significant effect on warfarin pharmacodynamics, as assessed by baseline-corrected maximum prothrombin time, time to maximum prothrombin time, and area under the prothrombin time-versus-time curve. The lack of pharmacokinetic or pharmacodynamic interaction observed in this study suggests that a clinically important effect of levofloxacin on warfarin is unlikely to occur during concurrent therapy.

RCT Entities:   Population Interventions Outcomes