ADENINE-ARABINOSIDE MONOPHOSPHATE COUPLED TO LACTOSAMINATED HUMAN ALBUMIN ADMINISTERED FOR 4 WEEKS IN PATIENTS WITH CHRONIC TYPE-B HEPATITIS DECREASED VIREMIA WITHOUT PRODUCING SIGNIFICANT SIDE-EFFECTS

A conjugate of adenine arabinoside monophosphate (ara-AMP) with the li ver-targeting molecule lactosaminated human serum albumin (L-HSA) was administered by intravenous infusion for 28 days to eight patients wit h chronic type B hepatitis. The daily dose varied among the patients, ranging hom 34 mg/kg to 53 mg/kg (equal to 1.5 and 2.3 mg/kg ara-AMP, respectively). Pharmacokinetic analysis indicated that, at every dose tested, the conjugate was disposed of without accumulation. Viral DNA serum levels fell markedly during treatment; values rose again when tr eatment was ceased. The L-HSA-ara-AMP conjugate did not cause either t he neurotoxic side effects of free ara-AMP or other adverse clinical r eactions. It produced a significant increase both in serum alkaline ph osphatase activity and platelet number, and a small but significant de crease in erythrocyte number. These laboratory parameters returned to normal levels within 2 months after treatment. The conjugate induced t he production of small amounts of antibodies (similar to 20 pmol of co njugate bound by 1 mL of serum) in one patient only. In conclusion, th e present results indicate that the L-HSA-ara-AMP conjugate can exert the antiviral activity of ara-AMP in chronic type B hepatitis patients without producing the neurotoxic side effects which hamper a 4-week p eriod of treatment with the free drug.