title: Pharmacokinetic/pharmacodynamic research on three different infusion time regimens of linezolid in healthy Chinese volunteers.
abstract: OBJECTIVE
  To evaluate the pharmacokinetic and pharmacodynamic (PK/PD) results of three different infusion time regimens of single doses of 600 mg linezolid in healthy Han Chinese volunteers.
  
  
  METHODS
  We conducted a clinical trial involving 6 male and 6 female healthy Chinese volunteers. They were randomized to receive intravenous linezolid infusion (600 mg/0.5 hours, 600 mg/2 hours, or 600 mg/4 hours) in three periods with washout periods of 7 days between each dosage. Serum linezolid concentration was measured in each subject at pre-dose (at 0 hours) until 24 hours after each dose. The ratio of the area under the serum concentration-time curve (AUC) to the minimum inhibitory concentration (MIC), AUC/MIC, was adopted as the major relevant parameter. Monte Carlo simulation was used to evaluate the probability of target attainment (PTA) of these three linezolid regimens.
  
  
  RESULTS
  One subject in 600 mg/0.5 hours regimen complained of mild pain at the injection site. No significant difference was found in pharmacokinetic parameters among the three different infusion regimens. When AUC/MIC was applied as parameter, PTA of 4 hours infusion regimen was much lower than that of the 0.5 hours and 2 hours infusion regimens (55.65% vs. 74.91% and 72.03%, respectively). Especially at higher MIC (2 μg/mL), the PTAs of the 0.5 hours and 2 hours infusion regimens decreased to 57.2% and 50.1%, respectively, while that of the 4 hours infusion regimen dropped sharply to only 25.95%. When T>MIC was applied as a parameter, PTA of the 0.5 hours regimen was higher than 90%, while the 2 hours and 4 hours regimens remained 100%.
  
  
  CONCLUSIONS
  Our findings suggest that 2 hours infusion of linezolid at a fixed dose (600 mg) regimen is appropriate to achieve the safety and efficacy against MRSA-caused infections in Chinese adults.
authors.forename: Yun
authors.initials: Y
authors.lastname: Cai
authors.forename: Nan
authors.initials: N
authors.lastname: Bai
authors.forename: Xu
authors.initials: X
authors.lastname: Liu
authors.forename: Beibei
authors.initials: B
authors.lastname: Liang
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
mesh_terms: D000081:Acetamides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D000328:Adult; D000890:Anti-Infective Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D000069349:Linezolid; D008297:Male; D008826:Microbial Sensitivity Tests; D009010:Monte Carlo Method; D023303:Oxazolidinones / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D014838:Volunteers
chemical_list: D000081:Acetamides; D000890:Anti-Infective Agents; D023303:Oxazolidinones; D000069349:Linezolid