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.

Penetration of prulifloxacin into sinus mucosa of patients undergoing paranasal sinus elective endoscopic surgery

“…1 It has the aptitude to penetrate several target tissues, [2][3][4] particularly lung tissue with a mean ratio of 6.9 between tissue and plasma concentrations, observed over a 24-hour period. 2 Following a single 600 mg oral administration of prulifloxacin, ulifloxacin reaches the maximum plasma concentration of 1.6 mg/ ml after 1 hour, with an AUC 0-' value of 7.3 mg/ml*h. 5 After 10-day repeated once daily administrations of prulifloxacin, the ulifloxacin C max was 2 mg/ml, with 0.75 hours and 7.6 mg/ml*h of t max and AUC ss corresponding values. 1 Unchanged ulifloxacin is predominantly eliminated via the kidneys, reaching very high urinary concentrations up to 48 hours after a single administration.…”

“…1 Unchanged ulifloxacin is predominantly eliminated via the kidneys, reaching very high urinary concentrations up to 48 hours after a single administration. 5 At the steady-state, achieved on the third treatment day, the binding to human serum proteins is 45%. 6 The elimination half-life is approximately of 10 hours.…”

Prulifloxacin versus Levofloxacin in the Treatment of Respiratory and Urinary Tract Infections: A Multicentre, Double-Blind, Randomized Controlled Clinical Trial

“…The pharmacokinetic properties of ulifloxacin in Chinese subjects have been studied previously. The results showed the terminal half-life of ulifloxacin to be approximately 7 h [11], which is similar to levofloxacin but shorter than that for Caucasian subjects (10–12 h) [12]. They also showed no accumulation in the plasma after receiving 264.2 mg twice daily for 7 days [11].…”

Prulifloxacin: a review focusing on its use beyond respiratory and urinary tract infections

“…Ulifloxacin is excreted mainly in the faeces, whilst a lower proportion is excreted in the urine [4,5]. This agent is mainly active against Gram-negative rods, including Pseudomonas aeruginosa but not Acinetobacter.…”