Linked Life Data

16293714

Source:http://linkedlifedata.com/resource/pubmed/id/16293714

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2006-2-23
pubmed:abstractText
Human immunodeficiency virus (HIV)-infected women have reduced exposure [area under the curve (AUC)] to anti-HIV protease inhibitors [e.g., nelfinavir (NFV)] during pregnancy. To determine the mechanistic basis of this phenomenon, we administered NFV mesylate orally (2.5 mg) or intravenously (0.625 mg) to timed pregnant (gestational age: 18-19 days) and non-pregnant FVB mice. After oral but not after i.v. administration, the plasma clearance of NFV was higher (by 134%, p < 0.05) and bioavailability was lower (by 32%, p < 0.05) in pregnant (n = 3) versus nonpregnant mice (n = 3). These effects of pregnancy were not due to changes in plasma protein binding of NFV. The half-life of NFV depletion in hepatic S-9 fractions of pregnant mice (n = 8) was 2.2-fold faster (p < 0.05) than that in nonpregnant mice (n = 7). Hepatic CYP3A activity (testosterone 6beta-hydroxylation, n = 4) and expression (n = 8) were significantly higher (by 138 and 49%, p < 0.05) in pregnant mice than that in nonpregnant mice. In the intestine, no CYP3A activity was detected and CYP3A protein expression (n = 6, p > 0.05) was not significantly different between the two groups. P-glycoprotein expression (n = 6) in hepatic and intestinal tissue of pregnant mice was not significantly different from that in nonpregnant mice. These changes in disposition of NFV during pregnancy are predominately due to a change in its bioavailability. An increase in hepatic CYP3A can explain the reduced bioavailability of NFV during pregnancy. If such upregulation of hepatic CYP3A activity occurs in pregnant women, it has important implications for dose adjustment of a variety of drugs ingested by pregnant women and cleared predominately via CYP3A metabolism.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
316
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1202-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Changes in pharmacokinetics of anti-HIV protease inhibitors during pregnancy: the role of CYP3A and P-glycoprotein.
pubmed:affiliation
Department of Pharmaceutics, University of Washington, Box 357610, Seattle, WA 98195, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural