Naslov
Can we individualize immunosuppression following renal transplantation - the pharmacogenomics of immunosuppressive agents

Autori
Božina, Nada

Vrsta, podvrsta i kategorija rada
Radovi u zbornicima skupova, cjeloviti rad (in extenso), znanstveni

Izvornik
44th Annual Scientific ESPN meeting / - , 2011

Skup
44th Annual Scientific ESPN meeting

Mjesto i datum
Cavtat, Hrvatska; Dubrovnik, Hrvatska, 14.09.2011. - 17.09.2011

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
immunosuppressive drugs; organ transplantation; genetics

Sažetak
Immunosuppressive drugs commonly used after organ transplantation to prevent acute rejection including cyclosporine, sirolimus, tacrolimus and mycophenolic acid are characterized by a narrow therapeutic index and broad interindividual variability in their pharmacokinetics. Data suggest that genetic prediction of the optimal initial drug dose leads to earlier attainment of target blood concentrations compared with using the standard initial dose. Some polymorphisms of genes involved in drug-metabolizing enzymes and transporter proteins have been associated with the pharmacokinetic and pharmacodynamic characteristics of immunosuppressive drugs. A few single nucleotide polymorphisms seem to have a significant impact on the incidence of acute rejection or the adverse effects of immunosuppressants. Environmental factors often interact with such genotype-phenotype relationships. The pharmacogenetic strategy that is closest to translation into clinical practice is the use of the cytochrome P450 (CYP)3A5 genotype to predict the optimal initial dose for tacrolimus. Other potential candidates are CYP3A5 and sirolimus and UGT1A9 and ABCC2 for mycophenolate. There are also genetic predictors of pharmacodynamics, including IMPDH1 for mycophenolate and ABCB1 for cyclosporine that may identify individuals at particular risk of efficacy failure or toxicity with a given drug. New published data suggest that carriers of the SLCO1B1*5 allele seem to be protected from MPA-related ADRs. The current level of evidence is not yet high enough to recommend pharmacogenetic personalization of immunosuppressive regimens in transplant recipients. The prevention of cellular toxicity associated with local metabolism or transport, which cannot be addressed by routine monitoring, is worth investigating further. Pharmacogenetic strategies offer promise as an adjunct to therapeutic drug monitoring in achieving target blood concentrations of the immunosuppressive drugs as early as possible after transplantation. As pharmacogenetic testing moves into routine clinical practice, standards for service delivery and reporting of results need to be established.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

POVEZANOST RADA