Single-dose pharmacokinetics and dose proportionality of intravenous pazufloxacin mesilate in healthy Korean volunteers

Objective: The aim of this study was to investigate the pharmacokinetics and dose proportionality of a single, intravenous dose of pazufloxacin mesilate, an injectable fluoroquinolone antibiotic, in healthy Korean male volunteers. Methods: In this open-label, four-dose, parallel study, subjects were randomized to receive a single dose of pazufloxacin mesilate 300, 500, 600, and 1,000 mg (n = 6, 20, 6, and 8, respectively) administered as a 1-h intravenous infusion. Blood and urine samples were collected serially from 0 to 24 h after drug administration and analyzed using a validated HPLC method. Tolerability was assessed by monitoring clinical laboratory parameters and adverse events. Results: After single-dose intravenous administration of pazufloxacin mesilate, the mean Cmax for groups treated with 300, 500, 600, and 1,000 mg doses ranged from 5.11 to 18.06 μg/mL; the mean AUC0-t ranged from 13.70 to 58.60 μg × h/mL. Pazufloxacin exhibits lack of dose proportionality over the dose range of 300 – 1,000 mg, based on linear regression model and power model. At all four dosages studied, pazufloxacin mesilate was well tolerated. Conclusions: Our data suggest that all regimens of pazufloxacin administration were well tolerated. Pazufloxacin exhibits lack of dose proportionality over the dose range of 300 – 1,000 mg.