[Clinical pharmacokinetics/pharmacodynamics study on pazufloxacin methanesulphonate injection].
OBJECTIVE
To identify rational dosage regimen for pazufloxacin methanesulphonate injection through a pharmacokinetics/pharmacodynamics (PK/PD) study.


METHODS
Pazufloxacin methanesulphonate at the doses of 300 mg and 500 mg were injected to 24 healthy volunteers. The plasma concentrations of pazufloxacin were measured by RPHPLC-UV. The MICs of pazufloxacin against 130 strains of 7 species of bacterias, as well as the MPCs of pazufloxacin against 5 species of bacterias were measured by double broth dilution method.


RESULTS
The AUC0-24/MIC50 of pazufloxacin methanesulphonate at a stabilized concentration state against methicillin-sensitive Staphylococcus aureus (MSSA) and S. pneumoniae were 215.36 and 107.68 at the dose of 300 mg, and 309.60 and 154.80 at the dose of 500 mg, respectively. The Cmax/MIC50 were 57.52 and 28.76 at the dose of 300 mg, and 81.28 and 40.64 at the dose of 500 mg, respectively. However, the AUC0-24/MIC of pazufloxacin methanesulphonate against methicillin-resistant staphylococcus aureus (MRSA) were far less than 40. Both the AUC0-24/MIC50 and the Cmax/MIC50 of pazufloxacin against P. aeruginosa at the doses of 300 mg and 500 mg exceeded the defined criteria 100 and 10. Whereas the AUC0-24/MIC and Cmax/MIC of pazufloxacin against E. coli, K. pneumoniae and A. baumanii were much less than 100 and 10. The capability of pazufloxacin methanesulphonate to prevent mutations of MSSA was strong at the dose of 500 mg, but not for other pathogenic bacteria either at 300 mg or 500 mg.


CONCLUSIONS
Pazufloxacin methanesulphonate at the dose of 300 mg and 500 mg have similar efficacy in treating acute bacterial infections. The dosage regimen of 300 mg Q12h intravenous infusion is recommended.
Wang
Xian-Gang
XG
Division of Clinical Pharmacology, West China Hospital, Sichuan University, Chengdu 610041, China.
Miao
Jia
J
Liang
De-Rong
DR
Yu
Qin
Q
Liang
Mao-Zhi
MZ
Zhang
Shu-Hua
SH
D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D010078:Oxazines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D013211:Staphylococcus aureus / Q000187:drug effects*; D055815:Young Adult
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D010078:Oxazines; C078052:pazufloxacin