Effects of probenecid and cimetidine on the pharmacokinetics of nemonoxacin in healthy Chinese volunteers

Drug Design, Development and Therapy

关键词: nemonoxacin;    probenecid;    cimetidine;    clinical pharmacokinetics;    drug-drug interaction;   

DOI  :  

来源: DOAJ

【 摘 要 】

Yi-fan Zhang,1 Xiao-jian Dai,1 Yong Yang,1 Xiao-yan Chen,1 Ting Wang,2 Yun-biao Tang,3 Cheng-yuan Tsai,4 Li-wen Chang,4 Yu-ting Chang,4 Da-fang Zhong1 1State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 2Department of Pharmacy, The First Hospital Affiliated to Lanzhou University, Lanzhou, 3Department of Pharmacy, The General Hospital of Shenyang Military Region, Shenyang, People’s Republic of China; 4TaiGen Biotechnology Co., Ltd., Taipei, Taiwan Purpose: 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.Conclusion: 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. Keywords: nemonoxacin, probenecid, cimetidine, clinical pharmacokinetics, drug–drug interaction 

【 授权许可】

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