Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Kniepeiss, D; Renner, W; Trummer, O; Wagner, D; Wasler, A; Khoschsorur, GA; Truschnig-Wilders, M; Tscheliessnigg, KH.
The role of CYP3A5 genotypes in dose requirements of tacrolimus and everolimus after heart transplantation.
Clin Transplant. 2011; 25(1): 146-150.
Doi: 10.1111/j.1399-0012.2009.01198.x
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- Führende Autor*innen der Med Uni Graz
- Kniepeiss Daniela
- Co-Autor*innen der Med Uni Graz
- Khoschsorur Gholamali
- Renner Wilfried
- Trummer Olivia
- Truschnig-Wilders Martini
- Tscheliessnigg Karlheinz
- Wagner Doris
- Wasler Andrae
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- Abstract:
- Background: tacrolimus and everolimus are immunosuppressive drugs metabolized by enzymes of the CYP3A subfamily. A common variant of the CYP3A5 gene, CYP3A5*3, results in strongly decreased CYP3A5 activity and has been shown to influence Tacrolimus blood concentrations, but its role for the pharmacogenetics of Everolimus remains unclear. Aim of the study was to examine the role of CYP3A5*3 variant in tacrolimus and everolimus dose and drug levels after heart transplantation. Methods: The present study comprised 15 patients with Tacrolimus and 30 patients with Everolimus-based maintenance therapy after heart transplantation. CYP3A5 genotypes were determined and correlated with clinical data. Results: In the Tacrolimus group, 13 subjects were CYP3A5 non-expressors (*3/*3 genotype) and two were heterozygous expressors (*1/*3 genotype). Average Tacrolimus dose was significantly higher in subjects expressing CYP3A5 compared to non-expressors. Tacrolimus levels were not significantly different at any point of time. In the Everolimus group, 27 subjects were CYP3A5 non-expressors (*3/*3 genotype) and three were heterozygous expressors (*1/*3). Neither Everolimus dose nor levels were significantly different between CYP3A5 expressors and non-expressors at any point of time. Discussion: We conclude that in adult patients after heart transplantation, CYP3A5 genotypes have a strong influence on Tacrolimus, but not Everolimus dose requirement.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Cytochrome P-450 CYP3A - genetics
- Dose-Response Relationship, Drug -
- Female -
- Follow-Up Studies -
- Genotype -
- Graft Rejection - diagnosis
- Heart Diseases - drug therapy
- Heart Transplantation -
- Humans -
- Immunosuppressive Agents - therapeutic use
- Male -
- Middle Aged -
- Pharmacogenetics -
- Polymorphism, Genetic - genetics
- Prognosis -
- Sirolimus - analogs and derivatives
- Tacrolimus - therapeutic use
- Find related publications in this database (Keywords)
- CYP3A5
- dose reduction
- genetic polymorphism
- heart transplantation