Urinary bactericidal activity, urinary excretion and plasma concentrations of gatifloxacin (400 mg) versus ciprofloxacin (500 mg) in healthy volunteers after a single oral dose

• Published in: International journal of antimicrobial agents 2004-03, Vol.23, p.6-16
• Main Authors: Boy, Dieter, Well, Michaela, Kinzig-Schippers, Martina, Sörgel, Fritz, Ankel-Fuchs, Dorothe, Naber, Kurt G
• Format: Article
• Language: English
• Subjects: Administration, Oral; Adult; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - blood; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - urine; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Bacteria - drug effects; Biological and medical sciences; Ciprofloxacin; Ciprofloxacin - administration & dosage; Ciprofloxacin - blood; Ciprofloxacin - pharmacology; Ciprofloxacin - urine; Cross-Over Studies; Escherichia coli; Female; Fluoroquinolones - administration & dosage; Fluoroquinolones - blood; Fluoroquinolones - pharmacology; Fluoroquinolones - urine; Gatifloxacin; Humans; Kinetics; Klebsiella pneumoniae; Male; Medical sciences; Metabolic Clearance Rate; Microbial Sensitivity Tests; Pharmacology. Drug treatments; Plasma concentration; Reference Values; Single oral dose; Urinary bactericidal activity; Urinary excretion
• ISSN: 0924-8579; 1872-7913
• DOI: 10.1016/j.ijantimicag.2003.09.006

In an open randomised double-crossover study 12 volunteers (six men, six women) received a single oral dose of gatifloxacin (400 mg) or ciprofloxacin (500 mg) to assess urinary bactericidal activity (in eight intervals up to 120 h) and pharmacokinetic (PK) parameters (up to 36 h). Plasma concentrations and urinary excretion were determined by HPLC with fluorescence detection, and urinary bactericidal titers (UBT) by microdilution-method, using antibiotic-free urine of each volunteer. The mean maximum plasma concentration of gatifloxacin was 3.35 mg/l and that of ciprofloxacin 2.12 mg/l. The mean (median) cumulative renal excretion of the parent drug was for gatifloxacin 81 (83)% of the administered dose within 120 h and for ciprofloxacin 43 (45)%. The UBTs, i.e. the highest two-fold dilution (antibiotic-free urine as diluent) of urine still being bactericidal, were determined for an Escherichia coli ATCC reference strain and nine clinical uropathogens with the following MICs (mg/l) for gatifloxacin/ciprofloxacin (microdilution, MHB): E. coli ATCC 25922 (0.008/0.008); E. coli 523 (0.06/0.06); Klebsiella pneumoniae 1058 (0.03/0.016); Proteus mirabilis 524 (0.125/0.016); Pseudomonas aeruginosa 561 (1/0.125); Enterococcus faecalis strains 60 an 55 (0.5/1 and 8/32); Staphylococcus aureus strains 248 and 596 (both 0.03/0.125) and S. saprophyticus Ho94 (0.125/0.25). The median UBTs measured within the first 6 h for gatifloxacin were between 1:16 and 1:≥1024 for the Gram-negative strains including P. aeruginosa and between 1:8 and 1:≥1024 for the five Gram-positive strains. The median UBTs for ciprofloxacin were between 1:64 and 1:≥1024 for the Gram-negative strains (incl P. aeruginosa) and between 1:1.5 and 1:768 for the five Gram-positive strains. The UBTs up to 12 h showed no difference ( P