Interchangeability of 400-mg intravenous and oral gatifloxacin in healthy adults.
OBJECTIVE
To evaluate the interchangeability of 400-mg intravenous and oral doses of gatifloxacin.


METHODS
Randomized, open-label, crossover study.


METHODS
GFI Pharmaceutical Services, Inc., Evansville, Indiana, USA.


METHODS
Twenty-four healthy men and women (12 of each gender), aged 18-42 years.


METHODS
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.


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.


CONCLUSIONS
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.
LaCreta
F P
FP
Department of Metabolism and Pharmacokinetics, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08540, USA.
Kaul
S
S
Kollia
G D
GD
Duncan
G
G
Randall
D M
DM
Grasela
D M
DM
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D018592:Cross-Over Studies; D005260:Female; D024841:Fluoroquinolones; D000077734:Gatifloxacin; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D000077734:Gatifloxacin