Clevudine (L-FMAU)

雪绒花

Clevudine is biochemically similar to DFIAU, but does not appear to have the associated problems of mitochondrial toxicity and lactic acidosis production, at least in vitro. Experiments in the infected woodchuck model have shown this drug to be highly active at a dose of 10mg per kg once daily, producing a 9 log decrease in viral load with a dose dependent delay in the time to viral recrudescence.

An open label phase I / II dose escalation study is underway, with patients receiving either 10mg, 50mg or 100mg once daily for 28 days. 24 of 25 individuals have completed the study protocol Median DNA reduction at day 28 was 2.48, 2.74 and 2.95 log10 copies/mL respectively. Interestingly, 5 months after the end of treatment the median decrease in HBV DNA was 1.91 log10 copies/mL in the 10mg arm, and 2.07 log10 copies/mL among individuals receiving 50mg of clevudine. In individuals who received 100mg once daily, data was only available to week 8 (one month post therapy cessation) with 5 available patients demonstrating a continued HBV DNA fall greater than 3 log10 copies/mL.

Reference
Selected Highlights from Drug Development for Antiretroviral Therapies 2001 (Hep DART 2001) [Abstract 039]
December 16-20, 2001, Maui, Hawaii