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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2008-3-19
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pubmed:abstractText |
The coadministration of protease inhibitors with anticancer drugs in the management of human immunodeficiency virus-related malignancies can cause potential drug-drug interactions. The effect of lopinavir/ritonavir (LPV/RTV) on the pharmacokinetics of irinotecan (CPT11) has been investigated in seven patients with Kaposi's sarcoma. Coadministration of LPV/RTV reduces the clearance of CPT11 by 47% (11.3+/-3.5 vs 21.3+/-6.3 l/h/m(2), P=0.0008). This effect was associated with an 81% reduction (P=0.02) of the AUC (area under the curve) of the oxidized metabolite APC (7-ethyl-10-[4-N-(5-aminopentanoic-acid)-1-piperidino]-carbonyloxycamptothecin). The LPV/RTV treatment also inhibited the formation of SN38 glucuronide (SN38G), as shown by the 36% decrease in the SN38G/SN38 AUCs ratio (5.9+/-1.6 vs 9.2+/-2.6, P=0.002) consistent with UGT1A1 inhibition by LPV/RTV. This dual effect resulted in increased availability of CPT11 for SN38 conversion and reduced inactivation on SN38, leading to a 204% increase (P=0.0001) in SN38 AUC in the presence of LPV/RTV. The clinical consequences of these substantial pharmacokinetic changes should be investigated.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenine,
http://linkedlifedata.com/resource/pubmed/chemical/Anti-HIV Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, Phytogenic,
http://linkedlifedata.com/resource/pubmed/chemical/Camptothecin,
http://linkedlifedata.com/resource/pubmed/chemical/Lamivudine,
http://linkedlifedata.com/resource/pubmed/chemical/Lopinavir,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphonic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrimidinones,
http://linkedlifedata.com/resource/pubmed/chemical/RPR 121056,
http://linkedlifedata.com/resource/pubmed/chemical/Ritonavir,
http://linkedlifedata.com/resource/pubmed/chemical/SN38-Glu,
http://linkedlifedata.com/resource/pubmed/chemical/irinotecan,
http://linkedlifedata.com/resource/pubmed/chemical/tenofovir
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1532-6535
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
83
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
601-6
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:17713471-Adenine,
pubmed-meshheading:17713471-Adult,
pubmed-meshheading:17713471-Aged,
pubmed-meshheading:17713471-Anti-HIV Agents,
pubmed-meshheading:17713471-Antineoplastic Agents, Phytogenic,
pubmed-meshheading:17713471-Antiretroviral Therapy, Highly Active,
pubmed-meshheading:17713471-Area Under Curve,
pubmed-meshheading:17713471-Camptothecin,
pubmed-meshheading:17713471-Drug Therapy, Combination,
pubmed-meshheading:17713471-European Continental Ancestry Group,
pubmed-meshheading:17713471-HIV Infections,
pubmed-meshheading:17713471-Humans,
pubmed-meshheading:17713471-Lamivudine,
pubmed-meshheading:17713471-Lopinavir,
pubmed-meshheading:17713471-Male,
pubmed-meshheading:17713471-Middle Aged,
pubmed-meshheading:17713471-Phosphonic Acids,
pubmed-meshheading:17713471-Pyrimidinones,
pubmed-meshheading:17713471-Ritonavir,
pubmed-meshheading:17713471-Sarcoma, Kaposi
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pubmed:year |
2008
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pubmed:articleTitle |
Lopinavir-ritonavir dramatically affects the pharmacokinetics of irinotecan in HIV patients with Kaposi's sarcoma.
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pubmed:affiliation |
Division of Experimental and Clinical Pharmacology, Department of Molecular Oncology and Translational Research, National Cancer Institute, Aviano, Italy.
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pubmed:publicationType |
Journal Article
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