Increasing cerebral bioavailability of drugs

• Main Authors: Moskowitz, Michael A, Liao, James K, Ron, Eyal S, Omstead, Mary Nallin
• Format: Patent
• Language: English
• Published: 16.11.2004

Compounds circulating in the bloodstream of vertebrates cannot freely diffuse into brain tissue due to the blood-brain barrier. This barrier is beneficial in protecting the brain from exogenous influences. However, this beneficial role can become detrimental in a situation requiring therapeutic intervention by a drug with a site of action in the brain, if that drug does not readily cross the blood-brain barrier. For instance, it may not be possible to administer a drug in high enough doses to elevate the systemic levels of the drug blood level sufficiently to achieve a brain blood level effective to produce a desired effect. This situation is particularly likely when the drug sought to be administered to the brain has toxic or unpleasant side effects to the remainder of the body. This problem is exacerbated if the condition requiring therapy is associated with a reduction in blood flow through the brain, such as that occurring due to an ischemic stroke or a cardiovascular event resulting in loss of blood pressure or restricted blood flow to the brain. A method and compositions are provided for increased cerebral bioavailability of blood-born compositions by administering the composition of interest while increasing brain NO levels. This increase in NO levels may be accomplished by stimulating increased production of NO by eNOS, especially by administering L-arginine, by administering agents that increase NO levels independent of ecNOS, or by any combination of these methods. As NO is increased, cerebral blood flow is consequently increased, and drugs in the blood stream are carried along with the increased flow into brain tissue. By increased flow, the site of action will be exposed to more drug molecules. By stimulating increased NO production, administration of drugs that are not easily introduced to the brain may be facilitated and/or the serum concentration necessary to achieve desired physiologic effects may be reduced.