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Norfloxacin does not alter warfarin's disposition or anticoagulant effect
M L Rocci1, P H Vlasses, L M Distlerath
1Department of Medicine, Jefferson Medical College, Philadelphia, PA 19107-5563.
Abstract:
Drug interactions related to inhibition of hepatic drug metabolism have been identified for some fluoroquinolone antibiotics. This study was designed to investigate whether the fluoroquinolone norfloxacin at the usual clinical dosage interacts with the anticoagulant agent warfarin. Ten healthy male subjects were administered a single oral dose of 30 mg warfarin sodium alone or during multiple-dose treatment with norfloxacin, 400 mg bid, in a randomized, crossover fashion. Plasma warfarin concentrations and prothrombin times were measured for 6 days after each of the two warfarin doses. The pharmacokinetic parameters of warfarin were comparable in the absence and presence of norfloxacin, including no significant differences in warfarin's elimination half-life, apparent total clearance, apparent volume of distribution, or peak plasma concentration. Norfloxacin also had no significant effect on the anticoagulant effect of warfarin, as assessed by the area under the prothrombin time versus time curve and the maximum response for prothrombin time. The lack of pharmacokinetic or pharmacodynamic interaction observed in this study suggests that a clinically important interaction of norfloxacin and warfarin is unlikely to occur in patients requiring both drugs.
Insights
Norfloxacin does not significantly affect warfarin pharmacokinetics or its anticoagulant effect. This fluoroquinolone antibiotic is unlikely to cause clinically important drug interactions with warfarin.
Area of Science:
- Pharmacology
- Drug Metabolism
- Clinical Pharmacy
Background:
- Fluoroquinolone antibiotics can inhibit hepatic drug metabolism, leading to potential drug interactions.
- The interaction between norfloxacin and warfarin, a common anticoagulant, requires investigation.
Purpose of the Study:
- To determine if norfloxacin interacts with warfarin at standard clinical doses.
- To assess the impact of norfloxacin on warfarin's pharmacokinetic and pharmacodynamic profiles.
Main Methods:
- A randomized, crossover study involving 10 healthy males.
- Administration of warfarin alone versus during multiple-dose norfloxacin treatment.
- Measurement of plasma warfarin concentrations and prothrombin times over 6 days.
Main Results:
- Norfloxacin did not significantly alter warfarin's elimination half-life, clearance, volume of distribution, or peak plasma concentration.
- No significant differences were observed in warfarin's anticoagulant effect (prothrombin time) with or without norfloxacin.
- Pharmacokinetic and pharmacodynamic parameters of warfarin remained comparable between treatment groups.
Conclusions:
- Norfloxacin is unlikely to cause clinically significant pharmacokinetic or pharmacodynamic interactions with warfarin.
- Concurrent use of norfloxacin and warfarin in patients may be safe without dose adjustments.
- Further clinical studies may confirm the safety profile in diverse patient populations.