Abstract |
With the aim of improving the chemotherapeutic index of 9-beta-D-arabinofuranosyl-adenine 5' monophosphate ( ara-AMP) in the treatment of chronic hepatitis B, this drug was conjugated with lactosaminated serum albumin (L-SA), a neoglycoprotein which only enters into hepatocytes. We used a L-SA- ara-AMP conjugate which, in contrast to those previously employed, has the advantage of remaining soluble after lyophilization. We found in mice that: (I) this new conjugate was quite stable in the bloodstream where only a small part of ara-AMP was released; (II) after administration of the conjugate labelled in the drug moiety both acid insoluble and soluble radioactivities were several times higher in liver than in other organs; (III) in mice with Ectromelia virus hepatitis, the conjugate inhibited virus DNA synthesis in liver without affecting cellular DNA synthesis in intestine and bone marrow; (IV) the conjugate did not display any recognizable sign of acute toxicity even at doses several fold higher than those pharmacologically active; and (V) when prepared with homologous albumin it was not immunogenic.
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Authors | L Fiume, B Bassi, C Busi, A Mattioli, G Spinosa |
Journal | Biochemical pharmacology
(Biochem Pharmacol)
Vol. 35
Issue 6
Pg. 967-72
(Mar 15 1986)
ISSN: 0006-2952 [Print] England |
PMID | 2420334
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Arabinonucleotides
- Pharmaceutical Vehicles
- Serum Albumin
- lactosaminated serum albumin
- Vidarabine Phosphate
- DNA
- Thymidine
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Topics |
- Animals
- Arabinonucleotides
(administration & dosage)
- Bone Marrow
(metabolism)
- DNA
(biosynthesis)
- Female
- Hepatitis B
(drug therapy)
- Intestinal Mucosa
(metabolism)
- Liver
(metabolism)
- Mice
- Pharmaceutical Vehicles
- Serum Albumin
(administration & dosage, metabolism)
- Thymidine
(metabolism)
- Vidarabine Phosphate
(administration & dosage, metabolism, toxicity)
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