BAŞARISIZ TEDAVİNİN OLASI SORUMLUSU: P GLİKOPROTEİNLER

P glikoprotein (P-gp) birçok ilaca karşı geliştirilen dirençten sorumlu MDR1 geninin ürünü olan bir efluks pompasıdır. Karaciğer, böbrek, ince bağırsak, kolon, beyin, kalp, periferal sinirler, plasenta, adrenal bezler ve testis gibi birçok dokudan izole edilmiştir. Kan-beyin ve kan-testis bariyeri gibi kan-doku bariyerlerinde, ince bağırsak, santral sinir sistemi, karaciğer ve böbrek gibi ilaç emilimi, dağılımı ve atılımında rol oynayan dokularda yüksek oranda bulunmakta olup ilaçların farmakokinetiğinde-toksikokinetiğinde kritik bir rol oynamaktadır. P-gp'in substratları olarak antimikrobiyaller, antineoplastikler, immünsupresanlar, HIV proteaz inhibitörleri, kardiyovasküler sistem ilaçları sayılabilir. P-gp'ler özellikle bazı kanser türlerinde görülen çoklu ilaç direncine sebep olmakta ve tedavi başarısızlıkla sonuçlanmaktadır. Bu derlemede P-gp'in yapısı, işlevi, sentezlenmesini etkileyen faktörler ve inhibitörleri özetlenmiştir. P-gp'in yapısı ve işlevinin anlaşılması bu ilaçlarla tedavi edilecek hastaların tedavi yaklaşımının planlanmasında faydalı olacaktır.

Reason for the Ineffective Treatment: P Glycoproteins

P glycoprotein (P-gp) is an efflux pomp that is production of MDR1 gene, responsible forresistance against lots of drug. P-gp is isolated from many tissues such as liver, kidney, smallintestine, colon, brain, heart, peripheral nervous system, placenta, adrenal glands and testis.P-gp occurs highly on small intestine, central nervous system, liver, kidney, blood-tissuebarriers and it plays a critical role in pharmacokinetics and toxicokinetics. Antimicrobials,antineoplastics, immunosuppressants, HIV protease inhibitors, cardiovascular system drugs areaccepted as P-gp substrates. P-gp's cause multiple drug resistance, especially in some typesof cancer, and treatment fails. Structure of P-gp, its function, its inhibitors and factors whichaffects its synthesis are summarized in this review. Disclosing structure of P-gp and its functioncan be useful for planning treatment of the patients to be treated with these drugs.

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