Linked Life Data

11302944

Source:http://linkedlifedata.com/resource/pubmed/id/11302944

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2001-4-16
pubmed:abstractText
P-Glycoprotein (Pgp) and cytochrome P450 3A (CYP3A) are important enzymes affecting the disposition of HIV protease inhibitors (HIV PIs). After multiple dosing experiments in rats, decreases in the plasma concentrations and area under plasma concentration-time curve (AUC) for HIV PIs have been observed. The purpose of these studies was to determine the changes in Pgp and CYP3A expression and HIV PI plasma exposure after multiple doses of HIV PIs. Male rats were orally dosed with an amprenavir prodrug (450 mg/kg/day amprenavir-equivalent) or nelfinavir (175 mg/kg/day) for 1 or 14 days. Relative to day 1, the C(max) and the AUC for amprenavir at day 14 were decreased by 33 and 51%, respectively. Similarly, the plasma concentration of nelfinavir at 1 h after the last dose (C(max)) was reduced by 52% after multiple doses. Compared with controls, dosing of amprenavir for 14 days increased intestinal Pgp and hepatic CYP3A protein levels by 59 and 151%, respectively, but did not alter intestinal CYP3A protein levels. In contrast, amprenavir treatment did not result in an increase in hepatic CYP3A activity. Nelfinavir treatment increased expression of intestinal Pgp and hepatic CYP3A levels by 83 and 85%, respectively, but not hepatic Pgp or intestinal CYP3A. HIV PIs also induced Pgp expression in the LS174T human intestinal cell line. These results indicate that HIV protease inhibitors induce both intestinal Pgp and hepatic CYP3A and suggest that induction of Pgp and CYP3A is a possible mechanism reducing drug exposure after multiple doses.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0090-9556
pubmed:author
pubmed:issnType
Print
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
754-60
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11302944-Animals, pubmed-meshheading:11302944-Anti-HIV Agents, pubmed-meshheading:11302944-Aryl Hydrocarbon Hydroxylases, pubmed-meshheading:11302944-Carbamates, pubmed-meshheading:11302944-Cytochrome P-450 CYP3A, pubmed-meshheading:11302944-Cytochrome P-450 Enzyme System, pubmed-meshheading:11302944-HIV Protease Inhibitors, pubmed-meshheading:11302944-Humans, pubmed-meshheading:11302944-Intestines, pubmed-meshheading:11302944-Liver, pubmed-meshheading:11302944-Male, pubmed-meshheading:11302944-Nelfinavir, pubmed-meshheading:11302944-Oxidoreductases, N-Demethylating, pubmed-meshheading:11302944-P-Glycoprotein, pubmed-meshheading:11302944-Rats, pubmed-meshheading:11302944-Rats, Wistar, pubmed-meshheading:11302944-Sulfonamides, pubmed-meshheading:11302944-Tumor Cells, Cultured
pubmed:year
2001
pubmed:articleTitle
Induction of P-glycoprotein and cytochrome P450 3A by HIV protease inhibitors.
pubmed:affiliation
Division of Bioanalysis and Drug Metabolism, Glaxo SmithKline, Inc., Research Triangle Park, NC 27709-3398, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't