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Effects of probenecid and cimetidine on the pharmacokinetics of nemonoxacin in healthy Chinese volunteers.
Drug Des Devel Ther. 2016; 10:357-70.DD

Abstract

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.

Authors+Show Affiliations

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People's Republic of China.State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People's Republic of China.State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People's Republic of China.State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People's Republic of China.Department of Pharmacy, The First Hospital Affiliated to Lanzhou University, Lanzhou, People's Republic of China.Department of Pharmacy, The General Hospital of Shenyang Military Region, Shenyang, People's Republic of China.TaiGen Biotechnology Co., Ltd., Taipei, Taiwan.TaiGen Biotechnology Co., Ltd., Taipei, Taiwan.TaiGen Biotechnology Co., Ltd., Taipei, Taiwan.State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People's Republic of China.

Pub Type(s)

Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26855561

Citation

Zhang, Yi-Fan, et al. "Effects of Probenecid and Cimetidine On the Pharmacokinetics of Nemonoxacin in Healthy Chinese Volunteers." Drug Design, Development and Therapy, vol. 10, 2016, pp. 357-70.
Zhang YF, Dai XJ, Yang Y, et al. Effects of probenecid and cimetidine on the pharmacokinetics of nemonoxacin in healthy Chinese volunteers. Drug Des Devel Ther. 2016;10:357-70.
Zhang, Y. F., Dai, X. J., Yang, Y., Chen, X. Y., Wang, T., Tang, Y. B., Tsai, C. Y., Chang, L. W., Chang, Y. T., & Zhong, D. F. (2016). Effects of probenecid and cimetidine on the pharmacokinetics of nemonoxacin in healthy Chinese volunteers. Drug Design, Development and Therapy, 10, 357-70. https://doi.org/10.2147/DDDT.S95934
Zhang YF, et al. Effects of Probenecid and Cimetidine On the Pharmacokinetics of Nemonoxacin in Healthy Chinese Volunteers. Drug Des Devel Ther. 2016;10:357-70. PubMed PMID: 26855561.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of probenecid and cimetidine on the pharmacokinetics of nemonoxacin in healthy Chinese volunteers. AU - Zhang,Yi-Fan, AU - Dai,Xiao-Jian, AU - Yang,Yong, AU - Chen,Xiao-Yan, AU - Wang,Ting, AU - Tang,Yun-Biao, AU - Tsai,Cheng-Yuan, AU - Chang,Li-Wen, AU - Chang,Yu-Ting, AU - Zhong,Da-Fang, Y1 - 2016/01/20/ PY - 2016/2/9/entrez PY - 2016/2/9/pubmed PY - 2016/10/12/medline KW - cimetidine KW - clinical pharmacokinetics KW - drug–drug interaction KW - nemonoxacin KW - probenecid SP - 357 EP - 70 JF - Drug design, development and therapy JO - Drug Des Devel Ther VL - 10 N2 - 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. SN - 1177-8881 UR - https://www.unboundmedicine.com/medline/citation/26855561/Effects_of_probenecid_and_cimetidine_on_the_pharmacokinetics_of_nemonoxacin_in_healthy_Chinese_volunteers_ L2 - https://dx.doi.org/10.2147/DDDT.S95934 DB - PRIME DP - Unbound Medicine ER -