Beyne İlaç Taşınması ve Dağılımının Farmakokinetiği

Year 2017, Issue: 2, 81 - 104, 01.06.2017

Tuğba Çopur Sibel Bozdağ Pehlivan Levent Öner

Abstract

Merkezi Sinir Sistemi MSS hastalıklarının sıklığında son zamanlarda ciddi bir artış görülmesi, bu alanda daha etkili ve güvenli tedaviler geliştirilmesi gerekliliğine yol açmıştır. İlaç keşfi ve geliştirilmesi çalışmalarında karşılaşılan en büyük zorluklardan biri beyinde etkili ve güvenli konsantrasyon profilinin elde edilmesidir. Farmakolojik etkinin ortaya çıkabilmesi için MSS ilaçlarının kan beyin engelini KBE geçmesi, hedef bölgeye etkili konsantrasyonlarda ulaşması ve ilacın serbest fraksiyonunun hedef ile uygun bir şekilde etkileşmesi gerekir. Serebral kan akım hızı F , KBE’nin permeabilitesi influks klerensi , ilacın fizikokimyasal özellikleri, beyin dokusuna nonspesifik bağlanma derecesi ve efluks klerensi beyne ilaç taşınmasında etkili olan temel faktörlerdir. Aktif influks ve/veya efluks taşıyıcılar da ilaçların mutlak beyin konsantrasyonunu etkiler. İlacın kan-beyin arasındaki dengelenme hızı CLin, Kin , dengelenme derecesi Kp,uu,beyin ve beyin içi dağılımı Vu,beyin ; beyinde etkili konsantrasyonlara ulaşıp ulaşmadığını doğrulamak için tespit edilmesi gereken başlıca parametrelerdir. Bu parametrelerin belirlenmesi için in vitro, in vivo ve in siliko yöntemler kullanılmaktadır.

Keywords

Kan-beyin engeli, beyne ilaç taşınması, farmakokinetik

Pharmacokinetics of Brain Drug Delivery and Distribution

Abstract

Recently, significant increases in the frequency of central nervous system CNS diseases have led to the need to develop more effective and safe therapies. One of the biggest challenges in drug discovery and development studies is obtained the effective and safe concentration profile in the brain. In order for pharmacologic efficacy to occur, CNS drugs must cross the bloodbrain barrier BBB , reach effective concentrations at the target site, and the free fraction of the drug should interact appropriately with the target. Cerebral blood flow F , permeability of BBB influx clearance , physicochemical properties of the drug, nonspecific binding level to the brain tissue and efflux clearance are the main factors that are effective in drug delivery to the brain. Active influx and/or efflux carriers also affect the absolute brain concentration of the drugs. The drug equilibrium rate CLin, Kin and the drug equilibrium extent Kp,uu,brain between blood to brain and intracerebral distribution of the drug Vu,brain are the main parameters which should be determined in order to verify whether the drug has reached effective concentrations in the brain or not. In vivo, in vitro and in silico methods are being used for the determination of such parameters.

Keywords

Blood-brain barrier, brain drug delivery, pharmacokinetics

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