國家衛生研究院 NHRI:Item 3990099045/1221
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    题名: Pharmacokinetics of anti-SARS-CoV agent niclosamide and its analogs in rats
    作者: Chang, YW;Yeh, TK;Lin, KT;Chen, WC;Yao, HT;Lan, SJ;Wu, YS;Hsieh, HP;Chen, CM;Chen, CT
    贡献者: Division of Biotechnology and Pharmaceutical Research
    摘要: Niclosamide has been demonstrated with inhibitory activity on the replication of SARS-CoV in Vero E6 cells. This study examined the pharmacokinetics and oral bioavailability of niclosamide and its two analogs, BPR1H366 and BPR1H369, in male Sprague-Dawley rats. After a single 2-mg/kg intravenous dose, the total body clearance (CL) of niclosamide, BPR1H366 and BPR1H369 was 20.0 +/- 2.9, 26.7 +/- 4.4 and 39.4 +/- 6.7 mL/kg/min, and the volume of distribution at steady state (Vss) was 0.9 +/- 0.4, 0.3 +/- 0.1 and 1.1 +/- 0.2 L/kg, respectively. The half-life (t(1/2)) of BPR1H366 and BPR1H369 was 2.6 +/- 0.3 and 3.7 +/- 1.1 hr, respectively, shorter than 6.7 +/- 2.0 hr of niclosamide. The AUC was 1413 +/- 118, 1019 +/- 203 and 750 +/- 113 ng/mL x hr for niclosamide, BPR1H366 and BPR1H369, respectively. After a single 5-mg/kg oral dose, all three compounds were rapidly absorbed. Niclosamide showed the highest C-max of 354 +/- 152 ng/mL within 30 min after oral gavage. The oral bioavailability of niclosamide, BPR1H366 and BPR1H369 was 10%, 12% and 15%, respectively. Our results demonstrated that the extents of drug exposure of the three compounds were comparable in rats. The pharmacokinetic properties of the compounds in humans are needed to be determined before their potential uses in SARS-CoV infected patients.
    关键词: Food Science & Technology;Pharmacology & Pharmacy
    日期: 2006-12
    關聯: Journal of Food and Drug Analysis. 2006 Dec;14(4):329-333.
    Link to: http://www.fda.gov.tw/publish_periodical.aspx?publish_periodicalsn=274&keyword=&classifysn=210&belongsn=214&periodicallistsn=4
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1021-9498&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000243186700003
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=33847011311
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