Central Nervous System Bioavailability

ALAN TALEVI; CAROLINA L. BELLERA

The ADME Encyclopedia. A Comprehensive Guide on Biopharmacy and Pharmacokinetics

Springer Nature

Año: 2022; p. 1 - 10

Due to multiple factors (including increased life expectancy and the adoption of lifestyles thatpromote the occurrence of affective/mood disorders), central nervous system (CNS) conditionsdisplay a growing incidence in modern society. A 2012 report by Murray et al. [1] compared thedisability-adjusted life years (DALYs) (resulting from the sum of years of life lost and years livedwith disability) for 291 health conditions, and for 187 countries, between 1990 and 2010,aggregating the data according to global and regional estimates. They observed that theDALYs per 1000 population decreased by 23% from 1990 to 2010, which suggests that in generalterms the health status of the world population improved in that period. However, globalDALYs (per 1,000,000 habitants) related to neurological and mood disorders (CNS conditions)increased 16.7% and 5.9%, respectively. By 2010, 10.4% of global DALYs arose from CNS conditions (3.0% from neurological disorders and 7.4% from affective disorders). Brain and CNS cancersalso showed an uptrend (1.3% increase). Mental and behavioral disorders are a major cause ofdisability, contributing as much as 36% at age 20?29 years [2]. Eight CNS conditions rankamong the top 25 global causes of disability,including major depressive disorder, anxiety,bipolar disorder, schizophrenia, epilepsy, and Alzheimer?s disease. The former figures do notinclude communicable health conditions that affect the CNS, such as meningitis or viralencephalitis. Disability due to CNS conditions keeps growing in the last years [3], which demonstrates the urgent need of new therapeutic approximations to neurological and psychiatricconditions. assuring CNS bioavailability is a critical step in the development of novel CNS drugcandidates, its back side is reducing CNS penetration for those drug categories intended forperipheral action, in order to reduce the probability of undesired central effects