Chemical structure of lamivudine.
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Lamivudine

Lamivudine (2',3'-dideoxy-3'-thiacytidine, 3TC) has the trade name EpivirĀ®. It is a potent reverse transcriptase inhibitor of the class nucleoside analog reverse transcriptase inhibitor (NARTI). more...

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Lamivudine has been used for treatment of chronic hepatitis B at a lower dose than for treatment of HIV. It improves the seroconversion of e-antigen positive hepatitis B and also improves histology staging of the liver. Long term use of lamivudine unfortunately leads to emergence of a resistant hepatitis B virus (YMDD) mutant. Despite this, lamivudine is still used widely as it is well tolerated.

History

Lamivudine was invented by Bernard Belleau and Nghe Nguyen-Ba at the Montreal-based IAF BioChem International, Inc. laboratories in 1989. The drug was later licensed to the British pharmaceutical company Glaxo for a 14 percent royalty.

Lamivudine was approved by the Food and Drug Administration (FDA) on Nov 17, 1995 for use with Zidovudine (AZT) and again in 2002 as a once-a-day dosed medication. The fifth antiretroviral drug on the market, it was the last NRTI for three years while the approval process switched to protease inhibitors. Its patent will expire in the United States on 2016-05-18.

Mechanism of action

Lamivudine is an analogue of cytidine. It can inhibit both types (1 and 2) of HIV reverse transcriptase and also the reverse transcriptase of hepatitis B. It needs to be phosphorylated to its triphosphate form before it is active. 3TC-triphosphate also inhibits cellular DNA polymerase.

Lamivudine is administered orally, and it is rapidly absorbed with a bio-availability of over 80%. Some research suggests that lamivudine can cross the blood-brain barrier. Lamivudine is often given in combination with zidovudine, with which it is highly synergistic. Lamivudine treatment has been shown to restore zidovudine sensitivity of previously resistant HIV. Several mutagenicity tests show that lamivudine should not show mutagenic activity in therapeutical doses.


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Lamivudine shows promise as hepatitis treatment - Brief Article
From Nutrition Health Review, 9/22/02

A 1998 study from Hong Kong, published in the New England Journal of Medicine (1998; 339:61), showed that lamivudine therapy leads to histologic and serologic improvement in patients with chronic hepatitis B. In 1999, a U.S. study involving 137 patients with chronic hepatitis B showed a decrease in inflammatory activity and a decrease in the likelihood of fibrosis while patients were undergoing treatment with lamivudine.

Most of the patients in the American study had undetectable serum hepatitis B virus (HBV) deoxyribonucleic acid (DNA) during the treatments, which lasted for one year. Four months after treatment was stopped, however, median HBV DNA levels had returned to about half the pretreatment value. There were no reported major side effects.

Lamivudine shows promise as a useful treatment for hepatitis B, but the length of required therapy and the impact on mortality are still unclear.

COPYRIGHT 2002 Vegetus Publications
COPYRIGHT 2003 Gale Group

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