Treatment of woodchuck hepatitis virus infection in vivo with 2', -3'-dideoxycytidine (ddC) and 2',-3'-dideoxycytidine monophosphate coupled to lactosaminated human serum albumin (L-HSA ddCMP).
Dideoxycytidine (ddC) is a nucleoside analogue active against human immunodeficiency virus and with in vitro activity against human hepatitis B virus. We investigated the ability of ddC to inhibit one of the Hepadnaviridae, the woodchuck hepatitis virus and compared the results with the effect obtained by a conjugate of lactosaminated human serum albumin 2',-3'-dideoxycytidine monophosphate (L-HSA ddCMP). This compound specifically enters the hepatocyte via the asialoglycoprotein receptor. We treated five chronic woodchuck hepatitis virus carriers with intravenous injections of 0.5 mg/kg body weight of ddC for 5 consecutive days, and under the same protocol five woodchucks with 10.4 mg/ kg L-HSA ddCMP, a dose equivalent to 0.25 mg/kg of free ddC. A reduction of serum woodchuck hepatitis virus DNA (5-125 fold) was observed during therapy in three out of five animals receiving ddC and in two of the five animals treated with L-HSA ddCMP. In responding woodchucks, virus DNA levels rebounded immediately after stopping therapy. No signs of toxicity were observed during or after the course of therapy. These preliminary results of short-term treatment indicate that ddC has anti-viral activity against woodchuck hepatitis virus. When the dose was reduced by 50%, L-HSA ddCMP showed anti-viral activity to an even lesser degree.
Zahm
F E
FE
F.Hoffman La-Roche Ltd, Basel, Switzerland.
d'Urso
N
N
Bonino
F
F
Ponzetto
A
A
D000818:Animals; D004279:DNA, Viral / Q000097:blood; D003845:Deoxycytosine Nucleotides / Q000494:pharmacology / Q000627:therapeutic use*; D054306:Dideoxynucleotides; D004337:Drug Carriers; D005260:Female; D006509:Hepatitis B / Q000188:drug therapy*; D017919:Hepatitis B Virus, Woodchuck / Q000187:drug effects*; D008297:Male; D008392:Marmota; D012709:Serum Albumin / Q000008:administration & dosage; D014766:Viremia / Q000188:drug therapy / Q000382:microbiology; D014779:Virus Replication / Q000187:drug effects; D016047:Zalcitabine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D004279:DNA, Viral; D003845:Deoxycytosine Nucleotides; D054306:Dideoxynucleotides; D004337:Drug Carriers; D012709:Serum Albumin; C046912:lactosaminated serum albumin; C101329:2',3'-dideoxycytidine monophosphate; D016047:Zalcitabine