Open-label, nonrandomized study of the effects of gatifloxacin on the pharmacokinetics of midazolam in healthy male volunteers.
OBJECTIVE
To confirm findings from an in vitro study that showed gatifloxacin did not substantially inhibit cytochrome P450 (CYP) 3A4 model substrate metabolism.


METHODS
Open-label, nonrandomized trial.


METHODS
Clinical pharmacology unit.


METHODS
Fourteen healthy adult men.


METHODS
Using midazolam probe methodology, the clearance of midazolam in the presence of multiple-dose gatifloxacin was evaluated.


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.


CONCLUSIONS
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.
Grasela
D M
DM
Department of Clinical Pharmacology, Bristrol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000, USA.
LaCreta
F P
FP
Kollia
G D
GD
Randall
D M
DM
Uderman
H D
HD
D000328:Adult; D000890:Anti-Infective Agents / Q000494:pharmacology*; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004347:Drug Interactions; D024841:Fluoroquinolones; D000077734:Gatifloxacin; D006801:Humans; D008297:Male; D008874:Midazolam / Q000097:blood / Q000493:pharmacokinetics*; D008875:Middle Aged; D010089:Oxidoreductases, N-Demethylating / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012016:Reference Values
D000890:Anti-Infective Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D024841:Fluoroquinolones; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; D000077734:Gatifloxacin; D008874:Midazolam