New Insights on the Pharmacokinetics of Ulifloxacin After Administration of Prulifloxacin in Patients with Mild, Moderate and Severe Renal Impairment

• Published in: Drugs in R&D Vol. 18; no. 3; pp. 237 - 245
• Main Authors: Tellone, Valeria, Coppola, Paola, Ammendola, Marco, Di Loreto, Giorgio, Picollo, Rossella, Del Vecchio, Alessandra, Comandini, Alessandro, Garofolo, Fabio, Tongiani, Serena
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.09.2018; Springer Nature B.V
• Subjects: Administration, Oral; Adolescent; Adult; Aged; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - pharmacokinetics; Dioxolanes - administration & dosage; Dioxolanes - pharmacokinetics; Dose-Response Relationship, Drug; Electrocardiography; Female; Fluoroquinolones - administration & dosage; Fluoroquinolones - analysis; Fluoroquinolones - pharmacokinetics; Humans; Internal Medicine; Male; Medicine; Medicine & Public Health; Middle Aged; Original; Original Research Article; Pharmacokinetics; Pharmacology/Toxicology; Pharmacotherapy; Piperazines - administration & dosage; Piperazines - analysis; Piperazines - pharmacokinetics; Renal Insufficiency - drug therapy; Urine; Young Adult
• ISSN: 1174-5886; 1179-6901
• DOI: 10.1007/s40268-018-0245-9

Background The antibacterial agent prulifloxacin, a prodrug of ulifloxacin, is indicated in the treatment of acute lower urinary tract infections, acute exacerbation of chronic bronchitis and acute bacterial rhinosinusitis. Objective We aimed to provide new insights on the pharmacokinetics (PK) of ulifloxacin in patients with different degrees of renal impairment. Methods A two-site, international, open-label, parallel-group, single- and repeated-dose study was performed. The drug was administered as a single dose of 600 mg to subjects with normal renal function and patients with mild, moderate and severe renal impairment. Subsequently, the same dose was administered daily for 7 days to subjects with normal renal function and patients with mild and moderate renal impairment, while a dose of 300 mg was administered daily for 7 days to patients with severe renal impairment. Plasma and urine ulifloxacin levels were measured. Complete safety evaluation was performed. Results Exposure to ulifloxacin increased as renal function decreased due to a lower ulifloxacin clearance. Ulifloxacin PK were significantly changed only in patients with severe renal impairment. The amount of ulifloxacin excreted in urine over a 24-h dosing period was similar in subjects with normal renal function and patients with mild impaired renal function, but lower in those with moderate and severe renal impairment. Conclusion Our data show that prulifloxacin is a safe quinolone and is well tolerated in both subjects with normal renal function and patients with impaired renal function, requiring a minimal dosage adjustment only in patients with severe renal impairment.