Relationship of octanol/water partition coefficient and molecular weight to rat brain capillary permeability

Abstract

The rat brain capillary permeability coefficient was determined for 27 compounds. The relationship of permeability to octanol/water partition coefficient and molecular weight was found to be predictable for drugs with molecular weights less than 400.

Impact of transporter-mediated drug absorption, distribution, elimination and drug interactions in antimicrobial chemotherapy

“…56 These results suggest participation of some kind of efflux system in the BBB for ß-lactam antibiotics. The limited distribution into the central nervous system (CNS) of ß-lactam antibiotics after administration to humans, as well as animals, is due to (a) the limited, possibly molecular-size-dependent, ability to cross the barrier of CNS, the degree of plasma protein binding and ionization, 57 and/or (b) the efflux from CNS to blood via an active transport system. 58 As shown in Fig.…”

Cultured Brain Microvessel Endothelial Cells as In Vitro Models of the Blood-Brain Barrier

“…From in vivo studies, it has been well established that the permeability of these molecules across the BBB depends directly on their lipophilicity and inversely on their molecular size (Oldendorf 1974;Levin 1980;Cornford et al 1982). Rim and coworkers (1986) and Shah and coworkers (1989) established a positive correlation between lipid solubility of a drug and its permeability across bovine brain microvessel endothelial monolayers grown onto microporous membranes.…”

“…Many substances with CNS activity, including drugs of abuse, cross the BBB by simple passive diffusion (Oldendorf 1974;Levin 1980;Cornford et al 1982). Accordingly, the BBB plays an important role in regulating access of drugs of abuse to the brain.…”

From polymeric particles to multifunctional nanocapsules for biomedical applications using the miniemulsion process

“…Low molecular weight hydrophilic compounds (MW < 150 g mol À1 ) and hydrophobic compounds (MW < 400 g mol À1 ) can pass the cellular barrier by passive diffusion and enter the brain. 146 All other components are excluded from this path and remain in the blood stream. The p-glycoprotein efflux pump system effectively removes substances from the endothelial cells that are internalized by these cells if they are not recognized as essential for the brain metabolism and can therefore pass into the brain.…”