title: Effects of probenecid and cimetidine on the pharmacokinetics of nemonoxacin in healthy Chinese volunteers.
abstract: OBJECTIVE
  To investigate the effects of probenecid and cimetidine on the pharmacokinetics of nemonoxacin in humans.
  
  
  METHODS
  Two independent, open-label, randomized, crossover studies were conducted in 24 (12 per study) healthy Chinese volunteers. In Study 1, each volunteer received a single oral dose of 500 mg of nemonoxacin alone or with 1.5 g of probenecid divided into three doses within 25 hours. In Study 2, each volunteer received a single oral dose of 500 mg of nemonoxacin alone or with multiple doses of cimetidine (400 mg thrice daily for 7 days). The plasma and urine nemonoxacin concentrations were determined using validated liquid chromatography-tandem mass spectrometry methods.
  
  
  RESULTS
  Coadministration of nemonoxacin with probenecid reduced the renal clearance (CLr) of nemonoxacin by 22.6%, and increased the area under the plasma concentration-time curve from time 0 to infinity (AUC0-∞) by 26.2%. Coadministration of nemonoxacin with cimetidine reduced the CLr of nemonoxacin by 13.3% and increased AUC0-∞ by 9.4%. Coadministration of nemonoxacin with probenecid or cimetidine did not significantly affect the maximum concentration of nemonoxacin or the percentage of the administered dose recovered in the urine.
  
  
  CONCLUSIONS
  Although probenecid reduced the CLr and increased the plasma exposure of nemonoxacin, these effects are unlikely to be clinically meaningful at therapeutic doses. Cimetidine had weaker, clinically meaningless effects on the pharmacokinetics of nemonoxacin.
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People's Republic of China.
authors: Yi-Fan
authors: YF
authors: Zhang
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People's Republic of China.
authors: Xiao-Jian
authors: XJ
authors: Dai
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People's Republic of China.
authors: Yong
authors: Y
authors: Yang
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People's Republic of China.
authors: Xiao-Yan
authors: XY
authors: Chen
authors: Department of Pharmacy, The First Hospital Affiliated to Lanzhou University, Lanzhou, People's Republic of China.
authors: Ting
authors: T
authors: Wang
authors: Department of Pharmacy, The General Hospital of Shenyang Military Region, Shenyang, People's Republic of China.
authors: Yun-Biao
authors: YB
authors: Tang
authors: TaiGen Biotechnology Co., Ltd., Taipei, Taiwan.
authors: Cheng-Yuan
authors: CY
authors: Tsai
authors: TaiGen Biotechnology Co., Ltd., Taipei, Taiwan.
authors: Li-Wen
authors: LW
authors: Chang
authors: TaiGen Biotechnology Co., Ltd., Taipei, Taiwan.
authors: Yu-Ting
authors: YT
authors: Chang
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People's Republic of China.
authors: Da-Fang
authors: DF
authors: Zhong
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D044466:Asian People; D002853:Chromatography, Liquid; D002927:Cimetidine / Q000494:pharmacology*; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D011339:Probenecid / Q000494:pharmacology*; D015363:Quinolones / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D015363:Quinolones; D002927:Cimetidine; C543520:nemonoxacin; D011339:Probenecid
keywords: cimetidine; clinical pharmacokinetics; drug–drug interaction; nemonoxacin; probenecid