Pharmacokinetics of clinafloxacin after single and multiple doses

Clinafloxacin (CI-960) is a potent broad-spectrum, fluoroquinolone antibiot ic that has been studied for parenteral and oral administration in patients with serious infections. The objectives of these studies were to examine t he pharmacokinetics and safety of clinafloxacin following administration of single and twice-daily intravenous (i.v.) and oral doses to volunteers. Pl asma and urine samples were assayed by validated liquid chromatographic met hods, and pharmacokinetic parameter values were determined by noncompartmen tal methods. Safety was evaluated by clinical observation and laboratory te sts. Absorption was rapid after oral administration, with maximum concentra tions in plasma (C-max) generally occurring within 2 h. Concentrations in p lasma declined biexponentially, with an average terminal half-life of 4 to 6 h after single doses and 5 to 7 h after multiple doses. Increases in C-ma x and area under the concentration-time curves (AUC) were generally proport ional to the dose. The volume of distribution was much greater than total b ody water. Approximately 40 to 75% of the clinafloxacin doses were excreted unchanged into urine. Absolute bioavailability of orally administered clin afloxacin was approximately 90% and did not change with increasing dose. Th erefore, switching patients from i.v. to oral dosing should achieve similar concentrations in plasma. The tolerability of clinafloxacin was acceptable . No serious adverse events occurred. C-max values and minimum plasma clina floxacin concentrations during multiple dosing exceeded MICs for a wide ran ge of organisms.