Linked Life Data

15066665

Source:http://linkedlifedata.com/resource/pubmed/id/15066665

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2004-4-6
pubmed:abstractText
Posaconazole is an antifungal with a wide-spectrum of activity against common and emerging fungal pathogens. In this randomised, open-label, two-way crossover study, the potential for drug interactions with posaconazole via the cytochrome P450 (CYP450) enzyme pathway was evaluated. Thirteen subjects received posaconazole tablets (2 x 100 mg) once daily for 10 days or no treatment; following a 14-day washout period, subjects were crossed over to the alternate treatment. The inhibition spectra of posaconazole were examined using a cocktail of the following probe substrates: caffeine (CYP1A2), tolbutamide (CYP2C8/9), dextromethorphan (CYP2D6 and total CYP3A4), chlorzoxazone (CYP2E1), and midazolam (hepatic CYP3A4). Except for midazolam, which was intravenously infused on Day 10, the cocktail probes were administered simultaneously on Day 9 during both treatment periods. Blood and urine samples were collected at specified times to quantitate probe substrates and/or metabolites. Based on insignificant differences in mean probe ratios, posaconazole did not inhibit CYP1A2, 2C8/9, 2D6, or 2E1. However, the midazolam AUC((tf)) was higher in the posaconazole than no-treatment group (93.4 n gh/ml versus 51.4 ng h/ml, P<0.01), indicating inhibition of hepatic CYP3A4. Drug interactions mediated by various CYP450 are common with the currently available triazole antifungals, however these results suggest that posaconazole may have an improved and more narrow drug interaction profile (CYP3A4 only) compared with other triazoles.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0928-0987
pubmed:author
pubmed:issnType
Print
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
645-53
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Effect of posaconazole on cytochrome P450 enzymes: a randomized, open-label, two-way crossover study.
pubmed:affiliation
Schering-Plough Research Institute, K-15-2650, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. david.wexler@spcorp.com
pubmed:publicationType
Journal Article, Clinical Trial, Comparative Study, Randomized Controlled Trial