Povezanost odnosa koncentracija-doza takrolimusa i genetskog polimorfizma kod bolesnika sa transplantiranim bubregom

  • Nemanja Rančić Centre for Clinical Pharmacology; Medical Faculty Military Medical Academy, University of Defence, Belgrade, Serbia
  • Neven Vavić Centre for Transplantation of Solid Organs, Military Medical Academy, Belgrade, Serbia
  • Bojana Cikota-Aleksić Military Medical Academy, Institute for Medical Research, Belgrade, Serbia
  • Zvonko Magić Military Medical Academy, Institute for Medical Research, Belgrade, Serbia
  • Momir Mikov University of Novi Sad, Faculty of Medicine, Institute for Pharmacology, Novi Sad, Serbia
  • Dubravko Bokonjić National Poison Control Centre, Medical Faculty Military Medical Academy, University of Defense, Belgrade, Serbia
  • Zoran Šegrt Management of the Military Medical Academy, Medical Faculty Military Medical Academy, University of Defence, Belgrade, Serbia
  • Viktorija Dragojević-Simić Centre for Clinical Pharmacology; Medical Faculty Military Medical Academy, University of Defence, Belgrade, Serbia
DOI: https://doi.org/10.2298/VSP151230329R
Ključne reči: transplantacija bubrega;, takrolimus;, lekovi, odnos doza-reakcija;, polimorfizam, genetički.

Sažetak


Uvod/Cilj. Odnos koncentracija-doza takrolimusa, kao potencijalna strategija terapijskog monitoringa lekova, upućuje na to da se može koristiti kod bolesnika sa transplantiranim bubregom. Cilj ove studije je bio da ispita vezu između odnosa koncentracija-doza takrolimusa koji je sugerisan kao strategija terapijskog monitoring lekova i genskog polimorfizma gena koji kodiraju najznačajnije enzime, CYP3A5 i CYP3A4, kao i transporter P-glikoprotein, za metabolizam i eliminaciju takrolimusa. Metode. Studija je osmišljena kao prospektivna serija slučajeva, u kojoj je jedinica monitoringa bio ambulantni pregled 54 bolesnika sa transplantiranim bubregom. Genotipizacija je urađena na aparatu 7500 Real-Time PCR System za procenu za diskriminacije alela koja se bazira na TaqMаn® metodologiji. Rezultati. Bolesnici (n = 13) koji su lečeni sa manje od 2 mg takrolimusa na dan (0,024 ± 0,006 mg/kg/dan) imali su odnos koncentracija-doza takrolimusa veći od 150 ng/mL/mg/kg. U ovoj grupi, 84,62% bolesnika je imalo CYP3А5 *3*3 alele. Svi ovi bolesnici su imali CYP3А4 *1*1/*1*1B alele. Što se tiče ABCB1 C3435T gena, 30,77% bolesnika je imalo TT gensku varijantu, dok je 69,23% njih imalo CC i CT gensku varijantu. Zaključak. Odnos koncentracija-doza takrolimusa veći od 150 ng/mL/mg/kg je granična vrednost kod bolesnika sa transplantiranim bubregom koji može da ukaže na one bolesnike koji su spori CYP3A5 metabolizeri i/ili su sa disfunkcionalnim P-glikoproteinom.

Reference

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Objavljeno
2020/10/22
Broj časopisa
Vol. 75 Br. 2 (2018)
Rubrika
Originalni članak