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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
1997-6-2
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pubmed:abstractText |
Coadministration with the human immunodeficiency virus (HIV) protease inhibitor ritonavir was investigated as a method for enhancing the levels of other peptidomimetic HIV protease inhibitors in plasma. In rat and human liver microsomes, ritonavir potently inhibited the cytochrome P450 (CYP)-mediated metabolism of saquinavir, indinavir, nelfinavir, and VX-478. The structural features of ritonavir responsible for CYP binding and inhibition were examined. Coadministration of other protease inhibitors with ritonavir in rats and dogs produced elevated and sustained plasma drug levels 8 to 12 h after a single dose. Drug exposure in rats was elevated by 8- to 46-fold. A > 50-fold enhancement of the concentrations of saquinavir in plasma was observed in humans following a single codose of ritonavir (600 mg) and saquinavir (200 mg). These results indicate that ritonavir can favorably alter the pharmacokinetic profiles of other protease inhibitors. Combination regimens of ritonavir and other protease inhibitors may thus play a role in the treatment of HIV infection. Because of potentially substantial drug level increases, however, such combinations require further investigation to establish safe regimens for clinical use.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/9056009-1373595,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9056009-1803993,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9056009-2183354,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9056009-3378384,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9056009-3433801,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9056009-6383611,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9056009-7477167,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9056009-7477168,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9056009-7492104,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9056009-7529365,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9056009-7587966,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9056009-7637723,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9056009-7700387,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9056009-7708670,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9056009-7712122,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9056009-7771104,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9056009-7816094,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9056009-7824947,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9056009-7932573,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9056009-8171040,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9056009-8599114,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9056009-8613951,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9056009-8633817,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9056009-8673921,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9056009-8724039
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0066-4804
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pubmed:author |
pubmed-author:BaroldiP APA,
pubmed-author:DenissenJ FJF,
pubmed-author:GrannemanG RGR,
pubmed-author:HsuAA,
pubmed-author:KempfD JDJ,
pubmed-author:KukulkaM JMJ,
pubmed-author:KumarGG,
pubmed-author:LeonardJ MJM,
pubmed-author:MarshK CKC,
pubmed-author:McDonaldEE,
pubmed-author:NorbeckD WDW,
pubmed-author:PizzutiDD,
pubmed-author:PlattnerJ JJJ,
pubmed-author:RodriguesA DAD,
pubmed-author:SunEE
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pubmed:issnType |
Print
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pubmed:volume |
41
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
654-60
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:9056009-Animals,
pubmed-meshheading:9056009-Anti-HIV Agents,
pubmed-meshheading:9056009-Area Under Curve,
pubmed-meshheading:9056009-Cytochrome P-450 Enzyme System,
pubmed-meshheading:9056009-Dogs,
pubmed-meshheading:9056009-Drug Interactions,
pubmed-meshheading:9056009-Female,
pubmed-meshheading:9056009-HIV Protease Inhibitors,
pubmed-meshheading:9056009-Humans,
pubmed-meshheading:9056009-Male,
pubmed-meshheading:9056009-Rats,
pubmed-meshheading:9056009-Rats, Sprague-Dawley,
pubmed-meshheading:9056009-Ritonavir
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pubmed:year |
1997
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pubmed:articleTitle |
Pharmacokinetic enhancement of inhibitors of the human immunodeficiency virus protease by coadministration with ritonavir.
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pubmed:affiliation |
Department of Infectious Diseases Research, Abbott Laboratories, Illinois 60064, USA. Dale.J.Kempf@abbott.com
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pubmed:publicationType |
Journal Article
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