Source:http://linkedlifedata.com/resource/pubmed/id/18520602
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
|
| pubmed:dateCreated |
2008-6-3
|
| pubmed:abstractText |
Liver disease may alter the pharmacokinetics of antiretrovirals and produce changes in plasma protein binding. The aim was to evaluate the pharmacokinetics of total and unbound lopinavir (LPV) in HIV-infected patients with and without hepatitis C virus (HCV) coinfection. Fifty-six HIV+ patients receiving lopinavir/ritonavir (LPV/r) (group I = 24 controls; II = 23 HIV/HCV-coinfected; III = 9 cirrhotic HIV/HCV-coinfected) were included. Total (n = 56) and unbound (n = 36) LPV pharmacokinetic parameters were determined at steady-state using validated high-performance liquid chromatography with ultraviolet detection and high-performance liquid chromatography-tandem mass spectrometry methods, respectively. Pharmacokinetic parameters (plasma concentration just before drug administration, peak concentrations in plasma, times to maximum plasma concentration, areas under the plasma concentration-time curve from 0 to 12 hours, and CL/F/kg) of both total and unbound LPV were calculated by standard noncompartmental methods and differences among groups evaluated (Kruskal-Wallis test).LPV apparent oral clearance normalized to body weight (median, interquartile range) was 55 (40-68), 59 (44-69), and 71 (53-78) mL/h/kg for groups I, II, and III, respectively (II vs. I, P = 0.52; III vs. I, P = 0.16). The areas under the plasma concentration-time curve from 0 to 12 hours were 110.4 (80.9-135.2), 103.4 (85.5-131.3), and 92.8 (87.4-116.3) microg h/mL for groups I, II, and III, respectively (II vs. I, P = 0.68; III vs. I, P = 0.71). Chronic liver impairment produced a slight, although not significant, decrease in plasma protein binding. The free-fraction of LPV increased ( approximately 21%) from 0.97% (0.80-1.06) in HIV+/HCV- patients to 1.18% (0.89-1.65) in HIV/HCV+ cirrhotic patients. The apparent oral clearance of unbound LPV (CLu/F/kg) in cirrhotic patients did not change significantly, supporting the concept that the clearance of unbound LPV in liver disease is not affected after being inhibited by low-dose ritonavir co-administration.LPV total and unbound pharmacokinetics were not affected by hepatic impairment, suggesting that no adjustment of LPV/r dose is required for HIV/HCV-coinfected patients with and without cirrhosis and moderate impairment of liver function.
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jun
|
| pubmed:issn |
0163-4356
|
| pubmed:author |
pubmed-author:BackDavid JDJ,
pubmed-author:CargnelAntoniettaA,
pubmed-author:CordierLauraL,
pubmed-author:CusatoMariaM,
pubmed-author:DickinsonLauraL,
pubmed-author:DucaPiergiorgioP,
pubmed-author:KhooSaye HSH,
pubmed-author:MeravigliaPaolaP,
pubmed-author:MicheliValeriaV,
pubmed-author:OrlandoGiovannaG,
pubmed-author:RegazziMarioM,
pubmed-author:RizzardiniGiulianoG,
pubmed-author:ViganòPaoloP,
pubmed-author:VillaniPaolaP
|
| pubmed:issnType |
Print
|
| pubmed:volume |
30
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
306-13
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| pubmed:dateRevised |
2011-11-17
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| pubmed:meshHeading |
pubmed-meshheading:18520602-Adult,
pubmed-meshheading:18520602-Area Under Curve,
pubmed-meshheading:18520602-Body Weight,
pubmed-meshheading:18520602-CD4 Lymphocyte Count,
pubmed-meshheading:18520602-Chromatography, High Pressure Liquid,
pubmed-meshheading:18520602-Female,
pubmed-meshheading:18520602-HIV Infections,
pubmed-meshheading:18520602-HIV Protease Inhibitors,
pubmed-meshheading:18520602-Hepatitis C,
pubmed-meshheading:18520602-Humans,
pubmed-meshheading:18520602-Liver Cirrhosis,
pubmed-meshheading:18520602-Liver Function Tests,
pubmed-meshheading:18520602-Lopinavir,
pubmed-meshheading:18520602-Male,
pubmed-meshheading:18520602-Middle Aged,
pubmed-meshheading:18520602-Prospective Studies,
pubmed-meshheading:18520602-Pyrimidinones,
pubmed-meshheading:18520602-Risk Factors,
pubmed-meshheading:18520602-Ritonavir,
pubmed-meshheading:18520602-Spectrophotometry, Ultraviolet,
pubmed-meshheading:18520602-Ultrafiltration
|
| pubmed:year |
2008
|
| pubmed:articleTitle |
Lopinavir/ritonavir pharmacokinetics in HIV/HCV-coinfected patients with or without cirrhosis.
|
| pubmed:affiliation |
II Department of Infectious Diseases - L. Sacco Hospital, Milan, Italy. v.micheli@hsacco.it
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| pubmed:publicationType |
Journal Article,
Clinical Trial,
Research Support, Non-U.S. Gov't
|