Abstract
The antimicrobial activity, absorption, excretion and clinical effect of pazufloxacin (PZFX), a newly developed quinolone derivative were studied, and the following results were obtained.
1) Antimicrobial activity
The antimicrobial activity of PZFX against 150 strains of clinically isolate was determined. The MIC90 of PZFX was 0.78μg/ml for methicillin-susceptible Staphylococcus aureus (MSSA), 3.13μg/ml for methicillin-resistant S. aureus (MRSA), 0.1μg/ml for Escherichia coli, 0.78μg/ml for Klebsiella pneumoniae, 0.2μg/ml for Proteus mirabilis and 6.25μg/ml for Pseudomonas aeruginosa.
2) Absorption and excretion
PZFX was administered to 3 healthy male adults at a single dose of 200 mg once, or 3 times a day after meals for 7 days, and the levels in saliva, sweat and urine were determined. The maximum blood level in the single dose study was 2.0-2.5μg/ml at 0.5-7 hours after administration, and 2.1-2.7μg/ml at 2-3 hours in the multiple dose study, showing no significant difference. Although transfer of this drug to saliva was almost as good as that to blood, the rate of transfer to sweat was slightly slower than that to blood.
The urinary recovery rate of PZFX in the single dose study was as high as 76.6-87.7% at 8 hours after administration, and no accumulation was observed in the multiple dose study.
The Cmax of PZFX in blood tended to be slightly lower when ingested with green tea or milk, however, it did not affect AUC or urinary excretion rate.
3) Clinical results
The clinical effect was evaluated in 11 patients including 5 with bacterial pneumonia, 3 with chronic bronchitis, 1 with acute pharyngitis, 1 with secondary infection of old pulmonary tuberculosis and 1 with infectious mononucleosis. PZFX was effective in 9 and unevaluable in 1, an efficacy rate of 90%. Bacteriologically, strains of S. aureus isolated from 2 patients with bacterial pneumonia and Streptococcus Pyogenes from 1 with acute pharyngitis were all eradicated. No objective or subjective side effects were observed except for 1 case each of mild elevation of GOT and platelet count on laboratory testing.
Thus, this drug was demonstrated to possess a wide antimicrobial spectrum and favorable pharmacokinetics, and proved to be a useful drug for infections in internal medicine.
