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.

Abstract

A conjugate of adenine arabinoside monophosphate (ara-AMP) with the liver-targeting molecule lactosaminated human serum albumin (L-HSA) was administered by intravenous infusion for 28 days to eight patients with chronic type B hepatitis. The daily dose varied among the patients, ranging from 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 treatment was ceased. The L-HSA-ara-AMP conjugate did not cause either the neurotoxic side effects of free ara-AMP or other adverse clinical reactions. It produced a significant increase both in serum alkaline phosphatase activity and platelet number, and a small but significant decrease in erythrocyte number. These laboratory parameters returned to normal levels within 2 months after treatment. The conjugate induced the production of small amounts of antibodies (approximately 20 pmol of conjugate bound by 1 mL of serum) in one patient only. In conclusion, the 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 period of treatment with the free drug.

• Authors: M Torrani Cerenzia, L Fiume, W De Bernardi Venon, B Lavezzo, M R Brunetto, A Ponzetto, G Di Stefano, C Busi, A Mattioli, G B Gervasi, F Bonino, G Verme
• Journal: Hepatology (Baltimore, Md.) (Hepatology) Vol. 23 Issue 4 Pg. 657-61 (Apr 1996) ISSN: 0270-9139 [Print] United States
• PMID: 8666314 (Publication Type: Journal Article)

Chemical References

• Antiviral Agents
• DNA, Viral
• Serum Albumin
• lactosaminated serum albumin
• Vidarabine Phosphate

Topics

• Adult
• Antiviral Agents (administration & dosage)
• Chronic Disease
• DNA, Viral (blood)
• Female
• Hepatitis B (drug therapy)
• Humans
• Male
• Middle Aged
• Serum Albumin (administration & dosage)
• Vidarabine Phosphate (administration & dosage, adverse effects, pharmacokinetics)
• Viremia (drug therapy)