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 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.
Torrani Cerenzia
M
M
Ospedale Molinette, Torino, Italy.
Fiume
L
L
De Bernardi Venon
W
W
Lavezzo
B
B
Brunetto
M R
MR
Ponzetto
A
A
Di Stefano
G
G
Busi
C
C
Mattioli
A
A
Gervasi
G B
GB
Bonino
F
F
Verme
G
G
D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D002908:Chronic Disease; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006509:Hepatitis B / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012709:Serum Albumin / Q000008:administration & dosage*; D001084:Vidarabine Phosphate / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D014766:Viremia / Q000188:drug therapy*
D000998:Antiviral Agents; D004279:DNA, Viral; D012709:Serum Albumin; C046912:lactosaminated serum albumin; D001084:Vidarabine Phosphate