Pharmacokinetics and pharmacodynamics of levofloxacin injection in healthy C hinese volunteers and dosing regimen optimization

Summary What is known and objective The pharmacokinetics ( PK ) and pharmacodynamics ( PD ) of levofloxacin were investigated following administration of levofloxacin injection in healthy C hinese 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 f C max /MIC ≥5 and f AUC 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 M onte C arlo simulation. The probability of target attainment ( PTA ) of levofloxacin at various minimal inhibitory concentrations ( MIC s) was also evaluated. Results and discussion 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 S treptococcus pneumoniae was 96·2% and 95·4%, respectively, in terms of f C max / MIC and f AUC / MIC targets. What is new and conclusion 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.