Comparative Pharmacokinetics of Ciprofloxacin, Gatifloxacin, Grepafloxacin, Levofloxacin, Trovafloxacin, and Moxifloxacin after Single Oral Administration in Healthy Volunteers

Abstract

ABSTRACT In an open, randomized, six-period crossover study, the pharmacokinetics of ciprofloxacin, gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin, and trovafloxacin were compared after a single oral dose in 12 healthy volunteers (6 men and 6 women). The volunteers received 250 mg of ciprofloxacin, 400 mg of gatifloxacin, 600 mg of grepafloxacin, 500 mg of levofloxacin, 400 mg of moxifloxacin, and 200 mg of trovafloxacin. The concentrations of the six fluoroquinolones in serum and urine were measured by a validated high-performance liquid chromatography method. Blood and urine samples were collected before and at different time points up to 48 h after medication. Levofloxacin had the highest peak concentration ( C max , in micrograms per milliliter) (6.21 ± 1.34), followed by moxifloxacin (4.34 ± 1.61) and gatifloxacin (3.42 ± 0.74). Elimination half-lives ranged from 12.12 ± 3.93 h (grepafloxacin) to 5.37 ± 0.82 h (ciprofloxacin). The total areas under the curve (AUC tot , in microgram-hours per milliliter) for levofloxacin (44.8 ± 4.4), moxifloxacin (39.3 ± 5.35), and gatifloxacin (30 ± 3.8) were significantly higher than that for ciprofloxacin (5.75 ± 1.25). Calculated from a normalized dose of 200 mg, the highest C max s (in micrograms per milliliter) were observed for levofloxacin (2.48 ± 0.53), followed by moxifloxacin (2.17 ± 0.81) and trovafloxacin (2.09 ± 0.58). The highest AUC tot (in microgram-hours per milliliter) for a 200-mg dose were observed for moxifloxacin (19.7 ± 2.67) and trovafloxacin (19.5 ± 3.1); the lowest was observed for ciprofloxacin (4.6 ± 1.0). No serious adverse event was observed during the study period. The five recently developed fluoroquinolones (gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin, and trovafloxacin) showed greater bioavailability, longer half-lives, and higher C max s than ciprofloxacin.