Open-label, nonrandomized study of the effects of gatifloxacin on the pharmacokinetics of midazolam in healthy male volunteers

Study Objective. To confirm findings from an in vitro study that showed gatifloxacin did not substantially inhibit cytochrome P450 (CYP) 3A4 model substrate metabolism. Design, Open-label, nonrandomized trial. Setting. Clinical pharmacology unit. Subjects. Fourteen healthy adult men. Intervention. Using midazolam probe methodology, the clearance of midazolam in the presence of multiple-dose gatifloxacin was evaluated. Measurements and Main Results. Typical steady-state concentrations of gatifloxacin 400 mg once/day had no effect on midazolam clearance, and gatifloxacin pharmacokinetics were unaffected by midazolam. All doses of both agents were well tolerated. Conclusion. Data from this in vivo trial support in vitro experience with gatifloxacin and suggest that interactions are unlikely between gatifloxacin and drugs that are metabolized by CYP3A.