Clinafloxacin Pharmacokinetics in Subjects with Various Degrees of Renal Function

Abstract

As the primary route for elimination of clinafloxacin is renal clearance (CL R ) of unchanged drug, studies were conducted to determine the pharmacokinetic profile of clinafloxacin following administration to young and elderly subjects, subjects with various degrees of renal function, and subjects requiring dialysis. These were open-label studies in which subjects received single oral clinafloxacin doses. Sixteen young subjects (18 to 35 years old) and 16 elderly subjects (>65 years old) were enrolled in a study comparing pharmacokinetic profiles of clinafloxacin in young and elderly subjects. Twenty subjects having various degrees of renal function were enrolled into one of three groups based on degree of renal function as measured by creatinine clearance (CL CR ). Twelve subjects with severe renal impairment requiring dialysis enrolled in a third study. Clinafloxacin was generally well tolerated by all subjects. Clinafloxacin pharmacokinetic profiles in elderly subjects were dependent only on age-related decreases in renal function. Clinafloxacin maximum concentrations in plasma, areas under the concentration-time curves, and terminal elimination half-life values increased with decreasing CL CR values. Total apparent body clearance of clinafloxacin from the plasma after oral administration (CL oral ) and CL R were dependent on CL CR according to the following relationships: CL oral ‫؍‬ 2.3 ⅐ CL CR ؉ 77 and CL R ‫؍‬ 1.74 ⅐ CL CR . Hemodialysis had no significant effect on clinafloxacin clearance. Based on the relationship between CL CR and clinafloxacin CL oral and CL R values, the clinafloxacin dose should be halved in patients having a CL CR of <40 ml/min. Further dose adjustment is not warranted in patients requiring hemodialysis.Clinafloxacin is an extremely potent member of the fluoroquinolone class of synthetic antimicrobial agents. Compared with available quinolone antibiotics, clinafloxacin usually requires lower drug concentrations for bacterial inhibition and is active against a broader spectrum of organisms. It is effective against many multiple-drug-resistant organisms, including quinolone-resistant strains (5,6,7,10,12,16). Clinafloxacin has been studied primarily in hospitalized adults for the treatment of serious and potentially life-threatening infections, including nosocomial pneumonia, community-acquired pneumonia, febrile neutropenia, complicated intra-abdominal infections, complicated skin and soft tissue infections, endocarditis, and acute gynecologic infections (16). It became apparent from initial clinical studies that twice-daily 100-to 400-mg doses were required to maintain concentrations in plasma within the effective range for most infections.Single and multiple-dose pharmacokinetics of clinafloxacin have been reported previously (2, 17). Following administration of 200-and 400-mg twice-daily intravenous doses, the mean total body clearance and volume of distribution values are approximately 320 ml/min and 156 liters, respectively, and the mean terminal elimination half-life (t 1/2 ) ...

Pharmacokinetics of Clinafloxacin Enantiomers in Humans

“…It is recommended that total clinafloxacin daily doses be reduced in patients having a Cl cr < 40 mL/min. 17 Similar changes were noted with enantiomer pharmacokinetic parameters following multiple doses in the 2 subjects with reduced Cl cr . Both enantiomers were extensively distributed after intravenous administration, which may explain the utility of clinafloxacin in treating multiple sites of infection.…”

Garenoxacin pharmacokinetics in subjects with renal impairment

“…These include fluoroquinolones that predominantly use renal elimination pathways (e.g., levofloxacin, ciprofloxacin, temafloxacin, and clinafloxacin) and those that favor non-renal elimination pathways (e.g., sparfloxacin eliminated via glucuronide metabolism, biliary excretion, and possibly intestinal secretion) [18][19][20][21][22] . Our results are similar to those reported for moxifloxacin in that no dosage adjustment is indicated in subjects with renal impairment.…”

Tigecycline Pharmacokinetics in Subjects With Various Degrees of Renal Function

“…Anti-infective therapy in patients with compromised renal function poses a therapeutic obstacle, sometimes requiring adjustment of dose or dosage interval, as well as attention to dialyzability [16][17][18][19][20][21][22] to match the pharmacodynamic profile associated with successful treatment of the infection of interest. Pharmacokinetic studies of anti-infective agents in subjects with renal impairment are crucial to determining the appropriate adjustment to doses necessary to match key pharmacodynamic parameters predictive of good clinical outcome.…”