Linked Life Data

2854453

Source:http://linkedlifedata.com/resource/pubmed/id/2854453

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1989-5-26
pubmed:abstractText
The acyclic guanosine analog (R,S)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine, (+/-)2HM-HBG, is an effective inhibitor of herpes simplex virus and varicella-zoster virus infections in vitro. This report is concerned with the pharmacokinetic evaluation of the drug in rats and monkeys and its antiviral activity in African green monkeys infected with simian varicella virus (SVV), a virus closely related to varicella-zoster virus that is also susceptible to inhibition by (+/-)2HM-HBG. Elimination half-lives in plasma following intravenous administration to monkeys (100 mumol/kg of body weight) ranged from 1.8 to 2.2 h, and total body clearance was 9.0 +/- 0.4 ml/min per kg (mean +/- standard error). After oral administration, levels in plasma were low, with a maximum concentration of the drug of only 3.1 +/- 0.8 microM, a time to reach maximum concentration of drug of 2.7 +/- 0.4 h, and an oral bioavailability of 10.6 +/- 1.4%. Because of the low oral bioavailability, SVV-infected monkeys were treated intramuscularly with (+/-)2HM-HBG. (+/-)2HM-HBG at a dosage of 10 mg/kg of body weight per day allowed moderate viremia, whereas a dosage of 30 mg/kg of body weight per day strongly suppressed viremia with minimal numbers of virus plaques from blood specimens collected at days 3, 5, and 7 postinfection and complete clearance at day 9 postinfection. Titers of antibody to SVV were also low. Treatment three times daily was somewhat more efficacious than treatment twice daily. Thus, (+/-)2HM-HBG is an effective inhibitor of SVV replication in vivo, despite the fact that leves of (+/-)2HM-HBG in plasma were low at extended periods of time and below the concentration of drug giving 50% inhibition of plaque formation obtained in vitro.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/2854453-192676, http://linkedlifedata.com/resource/pubmed/commentcorrection/2854453-2418021, http://linkedlifedata.com/resource/pubmed/commentcorrection/2854453-2823702, http://linkedlifedata.com/resource/pubmed/commentcorrection/2854453-2847643, http://linkedlifedata.com/resource/pubmed/commentcorrection/2854453-2990325, http://linkedlifedata.com/resource/pubmed/commentcorrection/2854453-3015006, http://linkedlifedata.com/resource/pubmed/commentcorrection/2854453-3024562, http://linkedlifedata.com/resource/pubmed/commentcorrection/2854453-3032092, http://linkedlifedata.com/resource/pubmed/commentcorrection/2854453-3040868, http://linkedlifedata.com/resource/pubmed/commentcorrection/2854453-3267458, http://linkedlifedata.com/resource/pubmed/commentcorrection/2854453-3872662, http://linkedlifedata.com/resource/pubmed/commentcorrection/2854453-6285700, http://linkedlifedata.com/resource/pubmed/commentcorrection/2854453-6299833, http://linkedlifedata.com/resource/pubmed/commentcorrection/2854453-6318659, http://linkedlifedata.com/resource/pubmed/commentcorrection/2854453-6711981, http://linkedlifedata.com/resource/pubmed/commentcorrection/2854453-6874878
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0066-4804
pubmed:author
pubmed:issnType
Print
pubmed:volume
32
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1807-12
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
1988
pubmed:articleTitle
Pharmacokinetics and antiviral activity in simian varicella virus-infected monkeys of (R,S)-9-[4-hydroxy-2-(hydroxymethyl) butyl]guanine, an anti-varicella-zoster virus drug.
pubmed:affiliation
Department of Antiviral Therapy, Research and Development, Astra Alab AB, Södertälje, Sweden.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.