The
drug concentrations in serum and urine were assayed by HPLC method and the pharmacokinetic parameters were calculated after
intravenous infusion of a single dose of 200 mg, 300 mg and 500 mg
levofloxacin to healthy volunteers. The in vitro activity MIC of
levofloxacin against 823 clinical isolates were determined and compared with other
antimicrobial agents. Based on the above results, the PK/PD parameters C(max)/MIC and AUC/MIC were calculated and the dosing regimens of
levofloxacin were proposed for
infections caused by different pathogens.
RESULTS: The results of clinical pharmacokinetic study showed that the C(max) of
levofloxacin was 3.4 mg/L +/- 0.8 mg/L, 4.8 mg/L +/- 1.4 mg/L and 7.6 mg/L +/- 1.1 mg/L respectively, AUC(0-infinity) was 14.4 mg.h/L +/- 2.5 mg.h/L, 21.9 mg.h/L +/- 4.5 mg.h/L and 38.3 mg.h/L +/- 4.9 mg.h/L respectively, T(1)/2 beta was 6.2 h +/- 0.4 h, 6.4 h +/- 0.9 h and 6.5 h +/- 0.6 h respectively, and 69% +/- 5%, 69% +/- 6%, and 65% +/- 4% of the doses were excreted in urine within 24 h after
intravenous infusion of a single dose of
levofloxacin 200 mg, 300 mg and 500 mg. The in vitro pharmacodynamic study showed that
levofloxacin was highly active against Hemolytic streptococcus and Moraxella catarrhalis. It was active against Streptococcus pneumoniae (including
penicillin nonsusceptible strains), Hemophilus influenzae,
methicillin-sensitive Staphylococcus aureus (MSSA), Klebsiella pneumoniae and Stenotrophomonas maltophilia.
Levofloxacin also had good activity against Pseudomonas aeruginosa and K.pneumoniae. However, most of isolates of enterococcal spp. were resistant to
levofloxacin. Above 50% of Escherichia coli isolates were resistant to
levofloxacin. Based on the results of PK/PD parameters, the adequate dosing regimens of
levofloxacin should be once daily 200 mg once daily of
levofloxacin was expected to be effective for the treatment of
infections caused by M. catarrhalis. The regimen of 300 mg once daily could be effective for the treatment of
infections caused by Hemolytic streptococcus. 500 mg once daily of
levofloxacin was expected to be effective for the treatment of
respiratory tract infections caused by S. pneumoniae or H. influenzae. For treatment of
respiratory tract infections and
urinary tract infections caused by
levofloxacin-susceptible organisms including K. pneumoniae, E. coli, P. aeruginosa, and S.maltophilia, 500 mg once daily of
levofloxacin was needed to obtain good clinical efficacy. But PK/PD parameters predicted that 500 mg daily of
levofloxacin was not effective for
infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and Enterococci.
CONCLUSION: