Özet:

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.

Anahtar Kelimeler: