Interchangeability of 400-mg intravenous and oral gatifloxacin in healthy adults

Study Objective. To evaluate the interchangeability of 400-mg intravenous a nd oral doses of gatifloxacin. Design. Randomized, open-label, crossover study. Setting. GFI Pharmaceutical Services, Inc., Evansville, Indiana, USA. Subjects. Twenty-four healthy men and women (12 of each gender), aged 18-42 years. Interventions. Subjects received single doses of gatifloxacin 400 mg either by intravenous infusion over 1 hour or a 400-mg tablet orally with 240 mi of water, each dose separated by a 1-week washout. Plasma concentrations of gatifloxacin were determined by a validated high-performance liquid chroma tography; pharmacokinetic parameters were calculated using noncompartmental methods. Distributions of pharmacokinetic parameter values were summarized by route of administration and gender. Effects of treatment on pharmacokin etic parameter values of gatifloxacin were assessed by an analysis of varia nce model suitable for a two-way, two-treatment, crossover design. Clinical evaluations were performed to assess drug safety and tolerability. Measurements and Main Results. Intravenous and oral gatifloxacin were consi dered interchangeable because both routes were bioequivalent with respect t o area under the curve (AUC; 90% confidence interval for the ratio of geome tric means contained within 0.8-1.25). The plasma concentration-time profil e after intravenous administration was similar and comparable in extent of exposure (AUC(0-infinity)) with that for the oral route when equal doses we re administered to men and women. The absolute bioavailability of gatifloxa cin after oral administration was 96%, consistent with bioequivalence of th e 400-mg intravenous and oral doses. The drug was well tolerated; the frequ ency of adverse events was comparable after intravenous and oral administra tion. Conclusion. Intravenous and tablet formulations of gatifloxacin are bioequi valent and therefore interchangeable. This permits greater flexibility in c hoosing oral or parenteral therapy with the possibility of avoiding hospita lization based on knowledge that oral administration will deliver therapeut ic exposure to the drug, or abbreviating hospital stay due to ease of switc hing from intravenous to oral therapy.