Minimizing Drug Exposure in the CNS while Maintaining Good Oral Absorption

In some drug discovery approaches, it is advantageous to restrict the access of compounds to the CNS to minimize the risk of side effects. By choosing appropriate physicochemical properties and building in the ability to act as substrates for active efflux transporters, it is possible to achieve CNS restriction and still retain sufficient absorption through the intestinal epithelium to retain good oral bioavailability. Potential risks in employing this approach are considered.