title: Safety and pharmacokinetics of dicloxacillin in healthy Chinese volunteers following single and multiple oral doses.
abstract: BACKGROUND
  Dicloxacillin, a semisynthetic isoxazolyl penicillin antibiotic, has antimicrobial activity against a wide variety of gram-positive bacteria including Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumonia, Streptococcus epidermidis, Streptococcus viridans, Streptococcus agalactiae, and Neisseria meningitidis. The objective of this study was to evaluate the safety and pharmacokinetic profile of dicloxacillin after single and multiple oral dose in healthy Chinese volunteers.
  
  
  METHODS
  A single-center, open-label, randomized, two-phase study was conducted in 16 subjects. In the single-dose phase, subjects were randomly assigned to receive single doses of 0.25, 0.5, 1.0, and 2.0 g of dicloxacillin sodium capsule in a 4-way crossover design with a 5-day washout period between administrations. In the multiple-dose phase, subjects were assigned to receive 0.25 or 0.5 g every 6 hours for 3 days in a 2-way crossover design. 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
  Following a single oral dose of 0.25-2.0 g dicloxacillin sodium, the maximum plasma drug concentration (Cmax) and the corresponding values for the area under the concentration- time curve from 0 to 10 hours (AUC0-10 h) increased in a dose-proportional manner. The mean elimination half-life (t1/2) was in the range of 1.38-1.71 hours. Dicloxacillin was excreted in its unchanged form via the kidney, with no tendency of accumulation, and varied from 38.65% to 50.10%. No appreciable accumulation of drug occurred with multiple oral doses of dicloxacillin. No serious adverse events were reported. Adverse events were generally mild.
  
  
  CONCLUSIONS
  Dicloxacillin was safe and well tolerated in the volunteers and displayed linear increases in the Cmax and AUC0-10 h values.
authors.affiliation: Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Guolan
authors.initials: G
authors.lastname: Wu
authors.affiliation: Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Yunliang
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Huili
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Xingjiang
authors.initials: X
authors.lastname: Hu
authors.affiliation: Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.affiliation: Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: You
authors.initials: Y
authors.lastname: Zhai
authors.affiliation: Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Meixiang
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Wu
authors.affiliation: Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Shentu
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D019540:Area Under Curve; D044466:Asian People; D002681:China; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004009:Dicloxacillin / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D064368:Healthy Volunteers; D006801:Humans; D016014:Linear Models; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D065667:Renal Elimination; D053719:Tandem Mass Spectrometry; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D004009:Dicloxacillin
keywords: dicloxacillin; healthy volunteers; pharmacokinetics; safety; tolerability