Page 147 - Interactive Theoritical Notes of Bioharmaceutics and pharamcokinetics.docx compressed

PharmD clinical pharmacy program Level 3, Semester 2 Biopharmaceutics & Pharmacokinetics (PT608(

To readily penetrate the brain, drugs must be:

✓ Fairly small and

✓ Lipid-soluble or

✓ Must be picked up by the carrier-mediated transport mechanism in the central

nervous system.

This explains why the small and highly fat-soluble anesthetic gases quickly and

easily penetrate the brain to cause anesthesia,

while other larger and water soluble molecules like penicillin antibiotics penetrate

the central nervous system to a much lesser degree.

Lipophilic compounds are able to enter the brain by passive transcellular

diffusion, but polar drugs are very difficult to enter brain tissue unless

transported by a specific carrier-mediated process.

In addition, distribution of lipophilic drugs to the brain is restricted by the

presence of efflux pumps in the lumenal membrane of the brain

endothelium.

These efflux pumps actively drive drugs such as chemotherapeutics from the

brain back to the blood and may thereby prevent significant distribution of

antitumor agents in the brain.

Metabolizing enzymes in the capillary endothelium may also break down a

drug before it can distribute into the brain.

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