A pharmacokinetic study on a novel anti-HBV agent imidol hydrochloride in rats.

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.