title: A pharmacokinetic study on a novel anti-HBV agent imidol hydrochloride in rats.
abstract: Imidol hydrochloride is a novel agent for the treatment of hepatitis B virus (HBV) infection, which is currently being evaluated in a phase II trial. This study investigated the absorption, excretion and tissue distribution of imidol after an oral dose in rats. The pharmacokinetic parameters were determined for both intravenous and oral dosing. A simple and sensitive UPLC-MS-MS method was employed to determine the imidol levels in rat biological samples. It was applied for the analysis of imidol in plasma, urine, feces, bile and various tissue samples. Imidol was found to have a moderate half-life (∼4 h), a relatively large apparent distribution volume and rapid clearance after an IV dose and oral doses up to 70 mg kg(-1). Dose-dependent linear relationships of AUC0-t and Cmax for imidol was found in the range of 10-70 mg kg(-1) after oral administration to rats. However, the oral bioavailability was low (17.6%). Most of the drug was metabolized and only 20% of the parent drug was excreted. Imidol excreted mainly in feces. The tissue distribution results show that imidol was quickly dispersed to various tissues following an oral dose. Relatively high concentration was found in liver, which is beneficial to the intended indication. Very low levels of imidol were found in brain and testes, indicating that it was difficult for imidol to cross the blood-brain barrier.
authors: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: liuzhongbo2008@sina.com.
authors: Zhongbo
authors: Z
authors: Liu
authors: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors: Ying
authors: Y
authors: Peng
authors: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors: Bingjie
authors: B
authors: Ma
authors: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors: Kashun
authors: K
authors: Bi
authors: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors: Yingchun
authors: Y
authors: Liu
authors: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors: Guoxiang
authors: G
authors: Sun
authors: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors: Gong
authors: G
authors: Ping
authors: School of Pharmacy, Fairleigh Dickinson University, Florham Park 07932, USA. Electronic address: yongguo@fdu.edu.
authors: Yong
authors: Y
authors: Guo
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D001812:Blood-Brain Barrier / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D006509:Hepatitis B / Q000188:drug therapy; D007211:Indoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D051381:Rats; D017208:Rats, Wistar; D013454:Sulfoxides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014018:Tissue Distribution
chemical_list: D000998:Antiviral Agents; D007211:Indoles; D013454:Sulfoxides; C571724:ethyl-6-bromo-5-hydroxy-4-(imidazol-1-yl)-methyl-1-methyl-2-(phenylsulfinylmethyl)-1H-indole-3-carboxylate
keywords: Absorption; Distribution; Excretion; HBV; Imidol; Rat