title: Pharmacokinetics of cefozopran by single and multiple intravenous infusions in healthy Chinese volunteers.
abstract: OBJECTIVE
  Cefozopran is a parenteral cephalosporin with a broad spectrum of activity against Gram-positive and Gram-negative bacteria. The objective of this study was to evaluate the pharmacokinetics of cefozopran after single- and multiple-dose intravenous administration in healthy subjects, to provide clinical guidance in its application.
  
  
  METHODS
  This was a single-center, open-label, randomized, two-phase study conducted in 12 subjects. In the single-dose phase, subjects were randomly assigned to receive single doses of 0.5, 1.0 and 2.0 g of injected cefozopran hydrochloride in a three-way crossover design with a 5-day washout period between administrations. In the multiple-dose phase, subjects received 2.0 g every 12 h for 4 days. Plasma and urine pharmacokinetic samples were assayed by a validated high-performance liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were calculated and analyzed statistically. Safety assessments were conducted throughout the study.
  
  
  RESULTS
  Twelve healthy volunteers (six males and six females) were enrolled and completed the study. Following a single 1-h intravenous infusion of 0.5, 1.0 or 2.0 g cefozopran, maximum plasma concentration (C max) and area under the plasma concentration-time curve from time zero to the time of the last measurable concentration (AUClast) increased in a dose-proportional manner. The mean half-life in plasma (t ½) was in the range of 1.20-2.80 h. Cefozopran was mainly excreted in its unchanged form, with no tendency for accumulation, via the kidney, and varied from 65.99 to 73.33 %. No appreciable accumulation of either drug occurred with multiple intravenous doses of cefozopran, and pharmacokinetic parameters for cefozopran were similar on days 1 and 4. No serious adverse events were reported. Adverse events were generally mild.
  
  
  CONCLUSIONS
  Cefozopran was safe and well tolerated in the volunteers and displayed linear increases in the C max and AUClast values.
authors: State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Research center of Clinical Pharmacy, First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79 Qingchun Road, 310003, Hangzhou, China.
authors: G L
authors: GL
authors: Wu
authors: J Z
authors: JZ
authors: Shentu
authors: H L
authors: HL
authors: Zhou
authors: M X
authors: MX
authors: Zhu
authors: X J
authors: XJ
authors: Hu
authors: J
authors: J
authors: Liu
authors: L H
authors: LH
authors: Wu
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D044466:Asian People; D002511:Cephalosporins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014018:Tissue Distribution; D055815:Young Adult; D000097586:Cefozopran
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D000097586:Cefozopran
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