Linked Life Data

19246722

Source:http://linkedlifedata.com/resource/pubmed/id/19246722

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2009-3-25
pubmed:abstractText
Given the prominent role of cytochrome P450 3A (CYP3A) in the metabolism of drugs, it is critical to determine whether new chemical entities will be affected by the inhibition of this enzyme system and result in clinically relevant drug interactions. Ketoconazole interaction studies are frequently performed to determine a given compound's sensitivity to CYP3A metabolism. The present study evaluated whether probing a sensitive substrate (midazolam) with a potent inhibitor (ketoconazole) at earlier time points (days 1 or 2) might be used to reliably gauge the magnitude of a meaningful interaction. The geometric mean ratios (ketoconazole+midazolamday 5/ketoconazole+midazolamday 1 and ketoconazole+midazolamday 5/ketoconazole+midazolamday 2) for midazolam AUC0-infinity were 1.36 and 1.06 with corresponding 90% confidence intervals of (1.17, 1.57) and (0.83, 1.23), respectively. These findings suggest that short-term drug-drug interaction studies can predict the magnitude of change in AUC as reliably as studies using longer duration treatments.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0091-2700
pubmed:author
pubmed:issnType
Print
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
398-406
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Effect of different durations of ketoconazole dosing on the single-dose pharmacokinetics of midazolam: shortening the paradigm.
pubmed:affiliation
Merck & Co, Inc, Whitehouse Station, NJ, USA. aubrey_stoch@merck.com
pubmed:publicationType
Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't