Ldc能有效抑制HBVDNA水平(2005.4.22)

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Valtorcitabine Effectively Suppresses HBV DNA Levels?br>

By Marina Nunez, MD, PhD

L-deoxycytidine (LdC) and L-thymidine (LdT, telbivudine) are small molecules which inhibit HBV polymerase. Valtorcitabine, a well-absorbed prodrug of LdC, has been shown to be synergistic with telbivudine for inhibiting HBV replication in vitro and in the woodchuck hepadnavirus model.

Valtorcitabine is being evaluated for development as anti-HBV drug to be given in combination with telbivudine.

In a randomized, double-blind, controlled, dose escalation Phase I/II study, the effects of seven doses of valtorcitabine given orally once-daily for 4 weeks were evaluated (50, 100, 200, 300, 600, 900, and 1,200 mg/day). Each group included 7 patients who had been randomized 6:1 to valtorcitabine or placebo.

Reductions in HBV DNA levels at day 28 correlated with doses from 50 mg/day (mean decrease -1.63 log10) to 900 mg/day (mean -3.04 log10). A diminished effect was seen with higher doses (1,200 mg/day).

Safety appeared comparable to placebo, with no treatment-related pattern of adverse events or laboratory abnormalities.

In their conclusions the authors stated that valtorcitabine demonstrated a good efficacy and safety profile for the treatment of patients with chronic hepatitis B. They further noted that a dose of 900 mg/day was selected for ongoing clinical evaluation in combination with telbivudine.

04/22/05

Reference S G Lim and others. Final results of a phase I/II dose escalation trial of valtorcitabine in patients with chronic hepatitis B. Abstract 34. 40th EASL. April 13-17, 2005. Paris, France.

特深沉

跟ldt同时开发的。早期的资料表明，药物公司打算用ldt,ldc联合使用，因为早期的研究表面，ldc效果

不如ldt显著。