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

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	Effects of probenecid and cimetidine on the pharmacokinetics of nemonoxacin in healthy Chinese volunteers
	Zhang, YF; Dai, XJ; Yang, Y; Chen, XY; Wang, T; Tang, YB; Tsai, CY; Chang, LW; Chang, YT; Zhong, DF
刊名	DRUG DESIGN DEVELOPMENT AND THERAPY
	2016
卷号	10 页码:357-370
关键词	nemonoxacin probenecid cimetidine clinical pharmacokinetics drug-drug interaction
ISSN号	1177-8881
文献子类	Article
英文摘要	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 (AUC(0-8)) by 26.2%. Coadministration of nemonoxacin with cimetidine reduced the CLr of nemonoxacin by 13.3% and increased AUC(0-8) 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.
学科主题	Pharmacology & Pharmacy
出版地	ALBANY
资助项目	国家科技重大专项
项目编号	National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program" of China [2012ZX0931-001]
语种	英语
WOS记录号	WOS:000368487900003
资助机构	MOST
内容类型	期刊论文
源URL	[http://ir.lzu.edu.cn/handle/262010/178542]
专题	第一临床医学院_期刊论文
通讯作者	Zhong, DF (reprint author), Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 501 Haike Rd, Shanghai 201203, Peoples R China.
推荐引用方式 GB/T 7714	Zhang, YF,Dai, XJ,Yang, Y,et al. Effects of probenecid and cimetidine on the pharmacokinetics of nemonoxacin in healthy Chinese volunteers[J]. DRUG DESIGN DEVELOPMENT AND THERAPY,2016,10:357-370.
APA	Zhang, YF.,Dai, XJ.,Yang, Y.,Chen, XY.,Wang, T.,...&Zhong, DF .(2016).Effects of probenecid and cimetidine on the pharmacokinetics of nemonoxacin in healthy Chinese volunteers.DRUG DESIGN DEVELOPMENT AND THERAPY,10,357-370.
MLA	Zhang, YF,et al."Effects of probenecid and cimetidine on the pharmacokinetics of nemonoxacin in healthy Chinese volunteers".DRUG DESIGN DEVELOPMENT AND THERAPY 10(2016):357-370.