Pharmacological and clinical profile of lamivudine (Zefix^®)

Abstract

Lamivudine ((-)-1-[(2R, 5S)-2-hydroxymethyl-1,3-oxathiolan-5-yl]cytosine, Zefix^®), one of the deoxycytidine derivatives, inhibits the HBV replication directly, and the mode of action of lamivudine has been proven to be its prevention of HBV-DNA synthesis in the transcription phase after conversion of lamivudine triphosphate in the cells. At 0.01-0.116 µM, lamivudine inhibits 50% of the virus production in in vitro studies. In the HBV infectious model (Trimera mice), the HBV-DNA level in serum was decreased in the lamivudine-treated group in comparison with the untreated group. In Phase III clinical trials, lamivudine therapy had a profound inhibitory effect on serum HBV-DNA-provoked HBe antigen resulting in rapid suppression viraemia and resolution of the progression of necro-inflammatory changes and fibrosis in the liver. Furthermore, lamivudine also has an excellent safety profile. Although lamivudine-resistant viruses emerged in the treatment of patients, the viruses had greatly impaired replication as compared with that of the wild-type virus. Thus, lamivudine is a useful agent for patients with persistent hepatitis B with virus proliferation and expected to be a novel chemotherapeutic drug.