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Profile of disposition, tissue distribution and excretion of the novel anti-human immunodeficiency virus (HIV) agent W-1 in rats.
Lu, Ying-Yuan; Wang, Xiao-Wei; Wang, Xin; Dai, Wen-Bing; Zhang, Qiang; Li, Pu; Lou, Ya-Qing; Lu, Chuang; Liu, Jun-Yi; Zhang, Guo-Liang.
Afiliação
  • Lu YY; Department of Pharmacology, School of Basic Medical Science, Beijing (Peking) University, No.38, Xue-Yuan Road, Beijing, 100191, People's Republic of China.
  • Wang XW; Department of Chemical Biology, School of Pharmaceutical Sciences, Beijing (Peking) University, Beijing, 100191, People's Republic of China.
  • Wang X; Department of Pharmacology, School of Basic Medical Science, Beijing (Peking) University, No.38, Xue-Yuan Road, Beijing, 100191, People's Republic of China.
  • Dai WB; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Beijing (Peking) University, Beijing, 100191, People's Republic of China.
  • Zhang Q; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Beijing (Peking) University, Beijing, 100191, People's Republic of China.
  • Li P; Department of Pharmacology, School of Basic Medical Science, Beijing (Peking) University, No.38, Xue-Yuan Road, Beijing, 100191, People's Republic of China.
  • Lou YQ; Department of Pharmacology, School of Basic Medical Science, Beijing (Peking) University, No.38, Xue-Yuan Road, Beijing, 100191, People's Republic of China.
  • Lu C; Department of Drug Metabolism & Pharmacokinetics, Biogen, MA, USA.
  • Liu JY; Department of Chemical Biology, School of Pharmaceutical Sciences, Beijing (Peking) University, Beijing, 100191, People's Republic of China.
  • Zhang GL; Department of Pharmacology, School of Basic Medical Science, Beijing (Peking) University, No.38, Xue-Yuan Road, Beijing, 100191, People's Republic of China. ZhangGL168@bjmu.edu.cn.
Arch Pharm Res ; 39(7): 970-7, 2016 Jul.
Article em En | MEDLINE | ID: mdl-27283844
The purpose of this study was to characterize the disposition, distribution, excretion and plasma protein binding of 6-benzyl-1-benzyloxymethyl-5-iodouracil (W-1) in rats. Concentrations of W-1 within biological samples were determined using a validated high performance liquid chromatography method. The plasma protein binding of W-1 was examined by equilibrium dialysis method. After oral administration of W-1 (50, 100 and 200 mg/kg, respectively) in self-microemulsifying drug delivery system formulation, the pharmacokinetic parameters of W-1 were as follows: the peak plasma concentrations (C max) were 0.42, 1.50 and 2.55 µg/mL, the area under the curve (AUC0-t) were 0.89, 2.27 and 3.96 µg/h mL and the plasma half-life (t 1/2) were 5.15, 3.77 and 3.77 h, respectively. Moreover, the prototype of W-1 was rapidly and extensively distributed into fifteen tissues, especially higher concentrations were detected in intestine, stomach and liver, respectively. The plasma protein binding of W-1 in rat, beagle dog and human were in the range of 97.96-99.13 %. This study suggested that W-1 has an appropriate pharmacokinetics in rats, such as rapid absorption, moderate clearance, and rapid distribution to multiple tissues. Those properties provide important information for further development W-1 as an anti-HIV-1 drug candidate.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: HIV-1 / Inibidores da Transcriptase Reversa / Fármacos Anti-HIV Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans / Male Idioma: En Revista: Arch Pharm Res Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: HIV-1 / Inibidores da Transcriptase Reversa / Fármacos Anti-HIV Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans / Male Idioma: En Revista: Arch Pharm Res Ano de publicação: 2016 Tipo de documento: Article