Source:http://linkedlifedata.com/resource/pubmed/id/17501760
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
|
| pubmed:dateCreated |
2007-5-15
|
| pubmed:abstractText |
This study investigated the molecular and pharmacokinetic mechanisms of the enhanced antiviral efficacy associated with pegylated interferon (PEG-IFN) alpha-2b and ribavirin. The study involved comparing the expression of serial double-stranded RNA-activated protein kinase (PKR) before and during treatment in 26 PEG-IFN alpha-2b and 26 conventional IFN alpha-2b recipients matched for age, body weight and dose of ribavirin. The pharmacokinetics of PEG-IFN alpha-2b and ribavirin was analysed in 15 of the 26 PEG-IFN recipients. There was a rapid increase in PKR expression in both treatment groups, although expression from day 2 onwards was maintained at a significantly higher level in the PEG-IFN recipients (P < 0.05). C(max) of PEG-IFN occurred 12-48 h after the initial administration, with t(1/2) and C(min) being 49 h and 190 pg/mL, respectively. In contrast to ribavirin, accumulation of PEG-IFN was minimal. There was no association between serum PEG-IFN and ribavirin levels and virological response. Although baseline expression of PKR before treatment was marginally higher in nonresponders (NRs), from day 2 onwards, sequential PKR expression in response to PEG-IFN was higher in sustained viral responders compared with the NRs (P < 0.05). Significant correlations were found between kinetics of PKR expression and viral decline rates in each phase of hepatitis C virus dynamics (first phase, r = 0.67, P = 0.0006; second phase, r = 0.67, P = 0.001). In conclusion, improvement in pharmacokinetics following pegylation led to higher intracellular PKR expression, which was associated with enhanced virological efficacy of PEG-IFN-based combination therapy. The concentrations of both ribavirin and PEG-IFN alpha-2b were not associated with viral response and PKR expression.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antiviral Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Polyethylene Glycols,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ribavirin,
http://linkedlifedata.com/resource/pubmed/chemical/eIF-2 Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/interferon alfa-2b,
http://linkedlifedata.com/resource/pubmed/chemical/peginterferon alfa-2b
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jun
|
| pubmed:issn |
1352-0504
|
| pubmed:author |
pubmed-author:AsahinaYY,
pubmed-author:DoiFF,
pubmed-author:HigakiMM,
pubmed-author:HosokawaTT,
pubmed-author:IzumiNN,
pubmed-author:KitamuraTT,
pubmed-author:KurosakiMM,
pubmed-author:MatsunagaKK,
pubmed-author:MiyakeSS,
pubmed-author:NakanishiHH,
pubmed-author:TsuchiyaKK,
pubmed-author:UchiharaMM,
pubmed-author:UedaKK,
pubmed-author:UmedaNN
|
| pubmed:issnType |
Print
|
| pubmed:volume |
14
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
396-403
|
| pubmed:dateRevised |
2011-11-17
|
| pubmed:meshHeading |
pubmed-meshheading:17501760-Administration, Oral,
pubmed-meshheading:17501760-Adult,
pubmed-meshheading:17501760-Aged,
pubmed-meshheading:17501760-Antiviral Agents,
pubmed-meshheading:17501760-Cells, Cultured,
pubmed-meshheading:17501760-Drug Therapy, Combination,
pubmed-meshheading:17501760-Female,
pubmed-meshheading:17501760-Gene Expression Regulation,
pubmed-meshheading:17501760-Hepacivirus,
pubmed-meshheading:17501760-Hepatitis C, Chronic,
pubmed-meshheading:17501760-Humans,
pubmed-meshheading:17501760-Injections, Intramuscular,
pubmed-meshheading:17501760-Injections, Subcutaneous,
pubmed-meshheading:17501760-Interferon-alpha,
pubmed-meshheading:17501760-Leukocytes, Mononuclear,
pubmed-meshheading:17501760-Male,
pubmed-meshheading:17501760-Middle Aged,
pubmed-meshheading:17501760-Polyethylene Glycols,
pubmed-meshheading:17501760-Polymerase Chain Reaction,
pubmed-meshheading:17501760-RNA, Messenger,
pubmed-meshheading:17501760-Recombinant Proteins,
pubmed-meshheading:17501760-Ribavirin,
pubmed-meshheading:17501760-Treatment Outcome,
pubmed-meshheading:17501760-Viral Load,
pubmed-meshheading:17501760-eIF-2 Kinase
|
| pubmed:year |
2007
|
| pubmed:articleTitle |
Pharmacokinetics and enhanced PKR response in patients with chronic hepatitis C treated with pegylated interferon alpha-2b and ribavirin.
|
| pubmed:affiliation |
Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
|
| pubmed:publicationType |
Journal Article,
Clinical Trial,
Randomized Controlled Trial,
Research Support, Non-U.S. Gov't
|