STUDY OBJECTIVE: To evaluate the interchangeability of 400-mg intravenous and 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 ml of water, each dose separated by a 1-week washout. Plasma concentrations of gatifloxacin were determined by a validated high-performance liquid chromatography; pharmacokinetic parameters were calculated using noncompartmental methods. Distributions of pharmacokinetic parameter values were summarized by route of administration and gender. Effects of treatment on pharmacokinetic parameter values of gatifloxacin were assessed by an analysis of variance 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 considered interchangeable because both routes were bioequivalent with respect to area under the curve (AUC; 90% confidence interval for the ratio of geometric means contained within 0.8-1.25). The plasma concentration-time profile after intravenous administration was similar and comparable in extent of exposure (AUC0-infinity) with that for the oral route when equal doses were administered to men and women. The absolute bioavailability of gatifloxacin after oral administration was 96%, consistent with bioequivalence of the 400-mg intravenous and oral doses. The drug was well tolerated; the frequency of adverse events was comparable after intravenous and oral administration. CONCLUSION: Intravenous and tablet formulations of gatifloxacin are bioequivalent and therefore interchangeable. This permits greater flexibility in choosing oral or parenteral therapy, with the possibility of avoiding hospitalization based on knowledge that oral administration will deliver therapeutic exposure to the drug, or abbreviating hospital stay due to ease of switching from intravenous to oral therapy.
RCT Entities:
STUDY OBJECTIVE: To evaluate the interchangeability of 400-mg intravenous and 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 ml of water, each dose separated by a 1-week washout. Plasma concentrations of gatifloxacin were determined by a validated high-performance liquid chromatography; pharmacokinetic parameters were calculated using noncompartmental methods. Distributions of pharmacokinetic parameter values were summarized by route of administration and gender. Effects of treatment on pharmacokinetic parameter values of gatifloxacin were assessed by an analysis of variance 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 considered interchangeable because both routes were bioequivalent with respect to area under the curve (AUC; 90% confidence interval for the ratio of geometric means contained within 0.8-1.25). The plasma concentration-time profile after intravenous administration was similar and comparable in extent of exposure (AUC0-infinity) with that for the oral route when equal doses were administered to men and women. The absolute bioavailability of gatifloxacin after oral administration was 96%, consistent with bioequivalence of the 400-mg intravenous and oral doses. The drug was well tolerated; the frequency of adverse events was comparable after intravenous and oral administration. CONCLUSION: Intravenous and tablet formulations of gatifloxacin are bioequivalent and therefore interchangeable. This permits greater flexibility in choosing oral or parenteral therapy, with the possibility of avoiding hospitalization based on knowledge that oral administration will deliver therapeutic exposure to the drug, or abbreviating hospital stay due to ease of switching from intravenous to oral therapy.
Authors: Christopher M Rubino; Edmund V Capparelli; John S Bradley; Jeffrey L Blumer; Gregory L Kearns; Michael Reed; Richard F Jacobs; Brenda Cirincione; Dennis M Grasela Journal: Antimicrob Agents Chemother Date: 2007-01-12 Impact factor: 5.191
Authors: Edmund V Capparelli; Michael D Reed; John S Bradley; Gregory L Kearns; Richard F Jacobs; Bharat D Damle; Jeffrey L Blumer; Dennis M Grasela Journal: Antimicrob Agents Chemother Date: 2005-03 Impact factor: 5.191
Authors: George G Zhanel; Kelly Ennis; Lavern Vercaigne; Andrew Walkty; Alfred S Gin; John Embil; Heather Smith; Daryl J Hoban Journal: Drugs Date: 2002 Impact factor: 9.546