Linked Life Data

15575918

Source:http://linkedlifedata.com/resource/pubmed/id/15575918

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2004-12-3
pubmed:abstractText
Everolimus, a proliferation signal inhibitor, is an immunosuppressant that targets the primary causes of progressive allograft dysfunction, thus improving the long-term outcome after heart transplantation. The present study investigated whether therapeutic drug monitoring (TDM) of everolimus would benefit heart transplant patients. Data from a twelve-month phase III trial comparing everolimus (1.5 or 3 mg daily) with azathioprine were used to evaluate everolimus pharmacokinetics, exposure-efficacy/safety and TDM prognostic simulations. Everolimus trough levels were stable in the first year post-transplant and averaged 5.2 +/- 3.8 and 9.4 +/- 6.3 ng/mL in patients treated with 1.5 and 3 mg/day, respectively. Cyclosporine trough levels were similar in all treatment groups. Biopsy-proven acute rejection (BPAR) was reduced with everolimus trough levels > or =3 ng/mL. Intravascular ultrasound (IVUS) analysis showed evidence of reduced vasculopathy at 12 months with increasing everolimus exposure. Unlike cyclosporine, increasing everolimus exposure was not related to a higher rate of renal dysfunction. The TDM simulation, which was based on two everolimus dose adjustments and an initial starting dose of 1.5 mg/day, showed that the simulated BPAR rate (with TDM) was 21% versus 26% in the group with fixed dosing. Therefore, TDM in heart transplantation could optimize immunosuppressive efficacy and reduce treatment-related toxicity.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1600-6135
pubmed:author
pubmed:issnType
Print
pubmed:volume
4
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2126-31
pubmed:dateRevised
2007-2-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Therapeutic drug monitoring for everolimus in heart transplant recipients based on exposure-effect modeling.
pubmed:affiliation
Department of Cardiovascular Medicine, Kaufman Center for Heart Failure, Cleveland, OH, USA. starlir@ccf.org
pubmed:publicationType
Journal Article, Clinical Trial, Comparative Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Multicenter Study, Clinical Trial, Phase III