Pharmacogenetic testing of CYP3A5 in optimization of initial tacrolimus dose for kidney transplant recipients

Gen CYP3A5 ima važnu ulogu u farmakokinetici takrolimusa, lijeka koji se koristi kao osnovna imunosupresivna terapija za bolesnike koji se podvrgavaju transplantaciji solidnih organa. Takrolimus je makrolidni antibiotik koji djeluje na principu inhibicije kalcineurinskog puta prijenosa signala. Cilj imunosupresivnog liječenja smanjenje je neželjenog imunosnog odgovora, ali ga prate i komplikacije. Pacijenti koji su ekspresori imaju izražen alel CYP3A5*1 te trebaju višu dozu takrolimusa u odnosu na neekspresore koji imaju izražen alel CYP3A5*3. Homozigoti CYP3A5*1/*1 i heterozigoti CYP3A5*1/*3 klasificiraju se kao brzometabolizirajući fenotip, odnosno intermedijarni metabolizatori. Takvi pacijenti zahtijevaju višu početnu dozu takrolimusa u odnosu na fenotip sporog metabolizatora CYP3A5*3/*3 koji trebaju standardnu preporučenu dozu. Prema smjernicama CPIC konzorcija, bolesnike na imunosupresivnom liječenju takrolimusom treba farmakogenetski testirati na točkastu mutaciju CYP3A5*3 prije početka terapije.The CYP3A5 gene plays an important role in the pharmacokinetics of tacrolimus, a drug used as primary immunosuppressive therapy for patients undergoing solid organ transplantation. Tacrolimus is a macrolide calcineurin inhibitor. Immunosuppressive therapy is intended to reduce the unwanted immune response, but also there are side-effects. It is important to minimize toxicity without risk of GVHD. Patients who are expressors have expressed CYP3A5*1 allele and need a higher dose of tacrolimus than non-expressors who have CYP3A5*3 allele expressed. Homozygotes CYP3A5*1/*1 and heterozygotes CYP3A5*1/*3 are classified as a rapidly metabolizing phenotype or intermediate metabolizers, respectively. These patients require a higher starting dose of tacrolimus compared to the phenotype of the slow metabolizer CYP3A5*3/*3, which need a standard dose. According to the guidelines of the CPIC consortium, patients on immunosuppressive therapy with tacrolimus should be pharmacogenetically tested for the CYP3A5*3 polymorphism prior to initiating the therapy

Pharmacogenetic testing of CYP3A5 in optimization of initial tacrolimus dose for kidney transplant recipients

Gen CYP3A5 ima važnu ulogu u farmakokinetici takrolimusa, lijeka koji se koristi kao osnovna imunosupresivna terapija za bolesnike koji se podvrgavaju transplantaciji solidnih organa. Takrolimus je makrolidni antibiotik koji djeluje na principu inhibicije kalcineurinskog puta prijenosa signala. Cilj imunosupresivnog liječenja smanjenje je neželjenog imunosnog odgovora, ali ga prate i komplikacije. Pacijenti koji su ekspresori imaju izražen alel CYP3A5*1 te trebaju višu dozu takrolimusa u odnosu na neekspresore koji imaju izražen alel CYP3A5*3. Homozigoti CYP3A5*1/*1 i heterozigoti CYP3A5*1/*3 klasificiraju se kao brzometabolizirajući fenotip, odnosno intermedijarni metabolizatori. Takvi pacijenti zahtijevaju višu početnu dozu takrolimusa u odnosu na fenotip sporog metabolizatora CYP3A5*3/*3 koji trebaju standardnu preporučenu dozu. Prema smjernicama CPIC konzorcija, bolesnike na imunosupresivnom liječenju takrolimusom treba farmakogenetski testirati na točkastu mutaciju CYP3A5*3 prije početka terapije.The CYP3A5 gene plays an important role in the pharmacokinetics of tacrolimus, a drug used as primary immunosuppressive therapy for patients undergoing solid organ transplantation. Tacrolimus is a macrolide calcineurin inhibitor. Immunosuppressive therapy is intended to reduce the unwanted immune response, but also there are side-effects. It is important to minimize toxicity without risk of GVHD. Patients who are expressors have expressed CYP3A5*1 allele and need a higher dose of tacrolimus than non-expressors who have CYP3A5*3 allele expressed. Homozygotes CYP3A5*1/*1 and heterozygotes CYP3A5*1/*3 are classified as a rapidly metabolizing phenotype or intermediate metabolizers, respectively. These patients require a higher starting dose of tacrolimus compared to the phenotype of the slow metabolizer CYP3A5*3/*3, which need a standard dose. According to the guidelines of the CPIC consortium, patients on immunosuppressive therapy with tacrolimus should be pharmacogenetically tested for the CYP3A5*3 polymorphism prior to initiating the therapy