Linked Life Data

8415401

Source:http://linkedlifedata.com/resource/pubmed/id/8415401

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1993-11-18
pubmed:abstractText
Didanosine is a purine nucleoside analogue approved for the treatment of human immunodeficiency virus infection. It is extremely unstable at pH values less than 3 and requires protection against gastric acid-induced hydrolysis. Beagle dogs pretreated with pentagastrin, an analogue of gastrin that reproducibly stimulates gastric acid secretion, have been used to screen different didanosine formulations. The absolute bioavailability of didanosine from a saline solution decreased from approximately 43% in untreated dogs to 8% after pretreatment with pentagastrin. Administration of buffered solution of didanosine to untreated and pretreated dogs yielded bioavailability estimates of 37 and 30%, respectively. In humans, the bioavailability from a similar buffered solution was approximately 40%. Pentagastrin-pretreated dogs were used to evaluate four new products relative to a citrate-phosphate buffer sachet, the formulation selected for large-scale clinical trials in humans. Two of these new formulations, a chewable tablet and an antacid suspension, were more bioavailable then the reference sachet. This also proved to be true in man, necessitating an adjustment in the dose of didanosine when administered as the chewable tablet. Dogs pretreated with pentagastrin accurately predicted the improved bioavailability of new didanosine formulations prior to clinical use. This animal model may be helpful in evaluating the biopharmaceutics of other acid-labile drugs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0724-8741
pubmed:author
pubmed:issnType
Print
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1157-64
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Biopharmaceutics of didanosine in humans and in a model for acid-labile drugs, the pentagastrin-pretreated dog.
pubmed:affiliation
Department of Metabolism and Pharmacokinetics, Bristol-Myers Squibb Company, Syracuse, New York 13221.
pubmed:publicationType
Journal Article, Clinical Trial, Randomized Controlled Trial