Pharmacokinetic Sanctuaries

The existence of the blood-brain barrier is an important consideration in the chemotherapy of neoplastic diseases of the brain or meninges. Poor drug penetration into the CNS has been a major cause of treatment failure in acute lymphocytic leukemia in children. Treatment programs for this disease now routinely employ craniospinal irradiation and intrathecally administered methotrexate as prophylactic measures for the prevention of relapses. The testes also are organs in which inadequate antitumor drug distribution can be a cause of relapse of an otherwise responsive tumor.

The multidrug transporter P-glycoprotein is expressed in the endothelial lining of the brain and testis but not in other organs and is thought to be a major component of the blood-brain and blood-testis drug barriers.

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