Clinical pharmacology of gatifloxacin, a new fluoroquinolone.
Gatifloxacin is an advanced-generation, 8-methoxy fluoroquinolone that is active against a broad spectrum of pathogens, including antibiotic-resistant Streptococcus pneumoniae. The drug has high oral bioavailability (96%), and, therefore, oral and intravenous formulations are bioequivalent and interchangeable. Gatifloxacin has a large volume of distribution ( approximately 1.8 L/kg), low protein binding ( approximately 20%), and broad tissue distribution and is primarily excreted unchanged in the urine (>80%). Gatifloxacin can be administered without dose modification in patients with hepatic impairment, in women, and in the elderly. In vitro experiments and clinical studies indicate that gatifloxacin does not interact with drugs metabolized by the cytochrome P450 enzyme family. At therapeutically relevant doses, gatifloxacin's pharmacodynamically linked parameters (the ratio of maximum serum concentration to minimum inhibitory concentration and the ratio of the area under the curve to minimum inhibitory concentration) are similar to or better than those of other fluoroquinolones. Clinical studies show that gatifloxacin has limited potential to prolong the QT interval on the electrocardiogram and lacks the potential to cause photosensitivity reactions, to alter oral glucose tolerance, or to cause crystalluria.
Grasela
D M
DM
Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543, USA. dennis.grasela@bms.com.
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D002412:Cations; D004347:Drug Interactions; D004361:Drug Tolerance; D005260:Female; D024841:Fluoroquinolones; D005502:Food; D000077734:Gatifloxacin; D006801:Humans; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008297:Male; D012449:Safety; D013810:Therapeutic Equivalency; D014018:Tissue Distribution
D000890:Anti-Infective Agents; D002412:Cations; D024841:Fluoroquinolones; D000077734:Gatifloxacin