The brain is protected from xenobiotic agents by the blood-brain barrier BBB. The BBB is a network of capilliaries lined by endothetial cells characterised by lack of fenestrations and very tight junctions between the cells. This restricts paracelleular diffusion of molecules, in addition there are a number of active transport mechanisms for transporting molecules into and more abundantly out of the brain. There are a number of energy dependent transporter proteins that are capable of binding to a wide variety of substrates and pumping them back into the plasma, perhaps the best known of which is multidrug resistance protein MDR.
A simple predictive model for blood-brain barrier penetration
Related to Barrier penetration: Quantum tunneling. In quantum mechanics, the passing of a particle through a seemingly impenetrable barrier without a cause that is explainable by classical physics. All rights reserved. Also, esp.
Barrier Penetration: A Concern for Armed Citizens?
Balamuthia mandrillaris, a free-living ameba, causes rare but frequently fatal granulomatous amebic encephalitis GAE. Few patients have survived after receiving experimental drug combinations, with or without brain lesion excisions. Some GAE survivors have been treated with a multi-drug regimen including miltefosine, an investigational anti-leishmanial agent with in vitro amebacidal activity. Miltefosine dosing for GAE has been based on leishmaniasis dosing because no data exist in humans concerning its pharmacologic distribution in the central nervous system. We describe results of limited cerebrospinal fluid CSF and serum drug level testing performed during clinical management of a child with fatal GAE who was treated with a multiple drug regimen including miltefosine.
Have you ever noticed how the indicated dosages for antimicrobials increase for CNS infections? This is because antimicrobials have a difficult time penetrating the blood brain barrier and the blood-CSF barrier, leading to difficulty of some antimicrobials to achieve therapeutic concentration levels in the CSF to properly treat a CNS infection. Disclaimer : the penetration of antimicrobials into the CSF is much more complicated than three columns and a list of antibiotics. Additionally, the treatment of CNS infections depends on more than just the CNS penetration of a certain antimicrobial, thus if any questions arise, please discuss with your ID consultants and ID pharmacists.