title: [Study of pharmacokinetics/pharmacodynamics of levofloxacin].
abstract: OBJECTIVE
  To evaluate the dosing regimens of levofloxacin.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  The proposed dosing regimens of levofloxacin based on PK/PD concepts are expected to provide good efficacy in clinical practice.
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Ji-cheng
authors.initials: JC
authors.lastname: Yu
authors.forename: Yao-guo
authors.initials: YG
authors.lastname: Shi
authors.forename: Le
authors.initials: L
authors.lastname: Zhou
authors.forename: Xin-yu
authors.initials: XY
authors.lastname: Ye
authors.forename: De-mei
authors.initials: DM
authors.lastname: Zhu
authors.forename: Ying-yuan
authors.initials: YY
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D001424:Bacterial Infections / Q000188:drug therapy*; D006801:Humans; D064704:Levofloxacin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D008826:Microbial Sensitivity Tests
chemical_list: D000900:Anti-Bacterial Agents; D064704:Levofloxacin