Pharmacokinetics and tolerability of prulifloxacin after single oral administration.

ABSTRACT

The pharmacokinetic properties and tolerability of three different strengths of prulifloxacin (CAS 123447-62-1), a new antibacterial agent prodrug of AF3013 (CAS 112984-60-8), have been investigated in a randomized, cross-over study performed in 12 Caucasian male subjects (age range 19-34 years). Prulifloxacin was administered as a single oral dose at the dosages of 300, 450 and 600 mg. Plasma concentrations of the active metabolite AF3013 were determined in blood samples collected before the administration (pre-dose) and at 15, 30, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 h after dosing. Urine samples were also collected. Determination in biological samples was performed using validated and specific HPLC methods. The following parameters were calculated Cmax, tmax, AUC0-t, AUC0--infinity, t1/2, V/F, Aeut, CLren and fe. The analysis of variance performed on dose-normalized data after logarithmic transformation evidenced no statistically significant differences between the three doses concerning Cmax and AUC. Friedman's test applied to tmax and t1/2 did not show any statistically significant difference between doses. A significant linear relationship between doses and AUC0-infinity was detected (p < 0.05). Very high urinary concentrations and the relatively long terminal half-life (10-12 h) suggest that a once-daily application would show adequate clinical efficacy, especially in urinary infections. The safety profile of the three doses was very good.