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Abstract
AbstractEntecavir (EV) is a first‐line antiretroviral agent to treat chronic hepatitis B. However, its oral administration is challenging, due to food effect on intestinal absorption. Therefore, in order to afford improved patient's compliance, a novel long‐acting injectable oil depot (OD) system of entecavir‐3‐palmiate (EV‐P), a lipidic ester prodrug of EV, was formulated. The OD consisted of oleic acid and benzyl alcohol as oily vehicles, with a suitable viscosity (38.6 centipoise with shear rate of 1 s−1). The prodrug was gradually released from the OD under sink conditions, providing delayed liberation than that by the hydrophilic parent compound. Following the intramuscular injection in rats, EV‐P OD provided a markedly protracted EV profile compared to oral EV; the EV levels in plasma were expanded over 2 weeks, with elimination half‐life of about 7 days. Therefore, we concluded that EV‐P OD can be a promising approach for a prolonged delivery of EV.
Published Version
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