title: Pharmacokinetics and pharmacodynamics of levofloxacin injection in healthy Chinese volunteers and dosing regimen optimization.
abstract: OBJECTIVE
  The pharmacokinetics (PK) and pharmacodynamics (PD) of levofloxacin were investigated following administration of levofloxacin injection in healthy Chinese volunteers for optimizing dosing regimen.
  
  
  METHODS
  The PK study included single-dose (750 mg/150 mL) and multiple-dose (750 mg/150 mL once daily for 7 days) phases. The concentration of levofloxacin in blood and urine was determined using HPLC method. Both non-compartmental and compartmental analyses were performed to estimate PK parameters. Taking fC(max) /MIC ≥5 and fAUC(24 h) /MIC ≥30 as a target, the cumulative fraction of response (CFR) of levofloxacin 750 mg for treatment of community-acquired pneumonia (CAP) was calculated using Monte Carlo simulation. The probability of target attainment (PTA) of levofloxacin at various minimal inhibitory concentrations (MICs) was also evaluated.
  
  
  CONCLUSIONS
  The results of PK study showed that the C(max) and AUC(0-∞) of levofloxacin were 14·94 μg/mL and 80·14 μg h/mL following single-dose infusion of levofloxacin. The half-life and average cumulative urine excretion ratio within 72 h post-dosing were 7·75 h and 86·95%, respectively. The mean C(ss,max), C(ss,min) and AUC(0-τ) of levofloxacin at steady state following multiple doses were 13·31 μg/mL, 0·031 μg/mL and 103·7 μg h/mL, respectively. The accumulation coefficient was 1·22. PK/PD analysis revealed that the CFR value of levofloxacin 750-mg regimen against Streptococcus pneumoniae was 96·2% and 95·4%, respectively, in terms of fC(max) /MIC and fAUC/MIC targets.
  
  
  CONCLUSIONS
  The regimen of 750-mg levofloxacin once daily provides a satisfactory PK/PD profile against the main pathogenic bacteria of CAP, which implies promising clinical and bacteriological efficacy for patients with CAP. A large-scale clinical study is warranted to confirm these results.
authors.affiliation: Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China.
authors.forename: G
authors.initials: G
authors.lastname: Cao
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: X
authors.initials: X
authors.lastname: Wu
authors.forename: J
authors.initials: J
authors.lastname: Yu
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: X
authors.initials: X
authors.lastname: Ye
authors.forename: D
authors.initials: D
authors.lastname: Zhu
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: B
authors.initials: B
authors.lastname: Guo
authors.forename: Y
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D004311:Double-Blind Method; D006207:Half-Life; D064368:Healthy Volunteers; D006801:Humans; D007262:Infusions, Intravenous; D064704:Levofloxacin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D064704:Levofloxacin
keywords: Monte Carlo simulation; healthy volunteer; levofloxacin; pharmacodynamics; pharmacokinetics