Linked Life Data

1798680

Source:http://linkedlifedata.com/resource/pubmed/id/1798680

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1992-4-15
pubmed:abstractText
We report the chemical and enzymatic hydrolysis of two hydrophobic prodrugs of ganciclovir (3 = dipropionate ester; 4 = diadamantoate ester). Both prodrugs undergo hydrolysis showing a pH dependence of kobs = kH+aH+ + ko + kHO-aHO- and a pH of maximum stability near pH 5. Only 4 exhibited a shelf life (t90) greater than 2 years. Compound 4 reacts significantly slower than ganciclovir in acidic media, even though the adamantyl esters provide additional reaction sites (which would be expected to increase the rate of degradation) that are distally removed from the guanine ring system, offering negligible steric or electronic substituent effects. Both 3 and 4 hydrolyzed in tissue homogenate, where kobs followed liver greater than intestine much greater than skin. Based on these findings of chemical stability, lipophilicity, and acceptable rate of enzymatic cleavage by skin esterases, 4 meets several of the criteria required for the topical sustained delivery of ganciclovir.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0724-8741
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1418-23
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
1991
pubmed:articleTitle
Chemical and enzymatic degradation of ganciclovir prodrugs: enhanced stability of the diadamantoate prodrug under acid conditions.
pubmed:affiliation
Genentech Inc., South San Francisco, California 94080.
pubmed:publicationType
Journal Article