PHARMACOKINETICS OF RUFLOXACIN IN HEALTHY-VOLUNTEERS AFTER REPEATED ORAL DOSES

Rufloxacin is a new broad-spectrum fluoroquinolone antibacterial agent. The pharmacokinetics and safety of rufloxacin were evaluated after repeated oral administration to healthy volunteers. The drug was administered once a day for 6 consecutive days following two different dose schedules. The first group of 11 subjects was given a loading dose of 300 mg on the first day and 150 mg on the subsequent 5 days. The second group of 12 subjects was given a loading dose of 400 mg and 200 mg for 5 days. Serum levels and urine concentrations of rufloxacin were determined by microbiological assay. A simultaneous fit of all data points for each subject was done according to a one-compartment open model. The drug was rapidly absorbed (absorption half-life 17 +/- 6 min in the 300 + 150 mg and 11 +/- 5 min in the 400 + 200 mg dose regimen group) and reached maximal serum concentrations (2.77 +/- 0.24 and 3.62 +/- 0.35-mu-g/ml) 4.2 +/- 0.4 and 4.0 +/- 0.9 h after the first administration. Steady-state serum concentrations (3.19 +/- 0.31 and 4.06 +/- 0.33-mu-g/ml) were reached in 3.7 +/- 0.7 and 4.5 +/- 0.4 days. Elimination half-lives were 29.5 +/- 2.4 and 36.0 +/- 2.8 h. Apparent volumes of distribution were 111 +/- 8 and 136 +/- 16 liters and apparent plasma clearances were 46 +/- 5 and 44 +/- 4 ml/min. Renal clearances were 18 +/- 3 and 17 +/- 2 ml/min. The percentage of the total dose excreted in urine throughout the study was 36.1 +/- 4.0% in the 300 + 150 mg and 43.7 +/- 2.5% in the 400 + 200 mg dose schedule group. Mean extents of accumulation were 2.4 +/- 0.2 and 2.5 +/- 0.1. Treatments were well tolerated, with only minor side effects (nausea, insomnia and postprandial vomiting) in 3 subjects and with no abnormalities being noted in routine laboratory examinations. Two and 3 days after the last administration, measurable antimicrobial activity was still observed in plasma and urine, indicating that the long half-life of rufloxacin assures valuable antibacterial coverage even after discontinuation of treatment.