Linked Life Data

12189360

Source:http://linkedlifedata.com/resource/pubmed/id/12189360

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2002-8-21
pubmed:abstractText
OBJECTIVE: Pharmacokinetic interactions are expected when human immunodeficiency virus (HIV) protease inhibitors are coadministered because many are both substrates for and inhibitors of CYP3A4. The goal of this model-based pharmacokinetic analysis was to describe the differences observed in amprenavir pharmacokinetics among treatment arms in the Adult AIDS Clinical Trial Group (AACTG) study protocol 398 and to propose mechanisms to account for them. METHODS: One hundred seventy-six HIV-positive subjects receiving 1200 mg amprenavir twice daily as part of AACTG protocol 398 were included in the pharmacokinetic study. All patients also received background medications efavirenz, adefovir dipivoxil, and abacavir and, depending on the study arm, placebo or one of the following protease inhibitors: nelfinavir, indinavir, or saquinavir. A population pharmacokinetic model was fitted to a total of 565 amprenavir concentration measurements. The blood samples for concentration measurements were drawn at week 2 (12-hour pharmacokinetic study, approximately 7 samples per study; 46 patients) and at week 24 (6-hour pharmacokinetic study, approximately 5 samples per study; 10 patients). In addition, samples were collected at 1 or more follow-up visits (population pharmacokinetic study, 1 to 3 occasions per patient; 150 patients). Results and Conclusion: Amprenavir intrinsic clearance was significantly reduced relative to placebo by nelfinavir (-41%) and indinavir (-54%) but not by saquinavir. The absolute magnitude of amprenavir intrinsic clearance suggests that CYP3A4 inhibition by nelfinavir and indinavir is balanced by enzymatic induction in the presence of the background drug(s), most likely efavirenz. Amprenavir intrinsic clearance apparently increases by more than 30% between weeks 2 and 24, possibly because of the time course of CYP3A4 induction.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/CYP3A protein, human, http://linkedlifedata.com/resource/pubmed/chemical/CYP3A4 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Carbamates, http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 CYP3A, http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 Enzyme System, http://linkedlifedata.com/resource/pubmed/chemical/HIV Protease Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Indinavir, http://linkedlifedata.com/resource/pubmed/chemical/Mixed Function Oxygenases, http://linkedlifedata.com/resource/pubmed/chemical/Nelfinavir, http://linkedlifedata.com/resource/pubmed/chemical/Saquinavir, http://linkedlifedata.com/resource/pubmed/chemical/Sulfonamides, http://linkedlifedata.com/resource/pubmed/chemical/amprenavir
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0009-9236
pubmed:author
pubmed:issnType
Print
pubmed:volume
72
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
133-41
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Effect of coadministration of nelfinavir, indinavir, and saquinavir on the pharmacokinetics of amprenavir.
pubmed:affiliation
Departments of Laboratory Medicine and Biopharmaceutical Sciences, University of California-San Francisco, San Francisco, CA 94143-0626, USA.
pubmed:publicationType
Journal Article, Clinical Trial, Research Support, U.S. Gov't, P.H.S., Controlled Clinical Trial, Research Support, Non-U.S. Gov't