Pradefovir, a New Agent for the Treatment of Chronic Hepatitis B?br>
By Marina Nunez, MD, PhD
Pradefovir (formerly remofovir) is a prodrug of PMEA, which contrary to adefovir (which is plasma esterase activated and achieves high concentrations in the kidney), is liver CYP3A4-activated, and therefore has lower potential nephrotoxicity.
In a phase I study performed in the US and Canada, 40 patients with detectable HBV DNA, either HBeAg+ or negative were randomized to receive 5, 10, 30 or 60 mg/day (N= 8 in each dose group) of pradofovir or placebo (N= 8) during 28 days, being followed for 12 weeks afterwards.
Most patients were of Asian origin (65%), and their mean HBV DNA and ALT levels were 7.3 to 7.6 log10 copies/mL and 51.8-124.3 IU/mL, respectively.
Pradofovir was rapidly and efficiently converted to PMEA. The Cmax and AUC for PMEA correlated with the dose of pradofovir. Steady state was achieved at day 9 of therapy.
Decreases in HBV DNA levels were of 2.06 log10 for the dose of 5 mg/day, 2.31 log10 for 10 mg/day, 2.54 log10 for 30 mg/day, and 2.98 log10 for the highest dose, 60 mg/day.
Side effects were mild and did not cause any drug discontinuation. The most frequently reported adverse event was headache among all patients.
In their conclusions the authors stated that pradofovir was safe and well tolerated for the treatment of chronic hepatitis B, inducing significant decreases in HBV DNA levels at the doses studied.
Phase II studies comparing pradefovir in combination with adefovir are currently underway.
04/22/05
Reference
D Lau and others. Safety, tolerability, pharmacokinetics and pharmacodynamics of remofovir in chronic HBV patients in USA and Canada following daily dosing for 28 days. Abstract 74. 40th EASL. April 13-17, 2005. Paris, France.
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发表于 2005-4-25 00:13
