Inhibition of hepatitis B virus replication by vidarabine monophosphate conjugated with lactosaminated serum albumin.
Vidarabine (ara A) produces severe dose-dependent side-effects. To examine whether its monophosphate ester (ara-AMP) can be effective in the treatment of chronic hepatitis B when given in reduced dosage as a conjugate with lactosaminated human serum albumin (L-HSA), which selectively enters hepatocytes, five patients with chronic type B hepatitis (HBsAg/HBV-DNA positive for at least 2 years) were treated with the conjugate. The daily dose of conjugate given (35 mg/kg) contains 1.5 mg ara-AMP, whereas the usual daily dose of free ara-AMP is 5-10 mg/kg. In three patients HBV-DNA fell to undetectable levels and remained negative in two; in one of them anti-HBe developed. In the other two patients HBV-DNA decreased but was detectable during treatment--one received three cycles of therapy, and became HBV-DNA negative and anti-HBe positive 45 days after the end of treatment; the other remained HBeAg/HBV-DNA positive. No adverse effects were observed, and biochemical variables (including aminotransferases) remained unchanged or decreased with viraemia. No antibodies (IgM and IgG classes) that bound the conjugate were detected. Thus L-HSA-ara-AMP inhibits HBV replication as well as free ara-AMP but at a third to a sixth of the dose.
Fiume
L
L
Department of Experimental Pathology, University of Bologna, Italy.
Cerenzia
M R
MR
Bonino
F
F
Busi
C
C
Mattioli
A
A
Brunetto
M R
MR
Chiaberge
E
E
Verme
G
G
D000328:Adult; D001088:Arabinonucleotides / Q000494:pharmacology*; D004279:DNA, Viral / Q000032:analysis; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005260:Female; D006509:Hepatitis B / Q000097:blood / Q000188:drug therapy*; D006515:Hepatitis B virus / Q000502:physiology*; D006521:Hepatitis, Chronic / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D012709:Serum Albumin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors; D001084:Vidarabine Phosphate / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D014779:Virus Replication / Q000187:drug effects*
D001088:Arabinonucleotides; D004279:DNA, Viral; D012709:Serum Albumin; C046912:lactosaminated serum albumin; D001084:Vidarabine Phosphate