Delivery of @entity1 interferon-alpha to brain by transient osmotic blood-brain barrier modification in the XXXX .

@entity1 @entity8639 @entity3027 @entity35
Pharmacokinetic parameters of @entity1 lymphoblastoid interferon ( @entity3027 ) delivery to normal @entity35 brain were examined. @entity3027 concentrations in brain parenchyma could only be detected 120 min after its intravascular administration, and were 0.003% per gram of the administered dose. The mean cerebrovascular permeability-surface area (permeability x surface area) product to IFN, 120 min after infusion, was 0.35 x 10(-6) @entity8639 , which is not significantly different from zero. Neither i.v. nor intracarotid @entity3027 administration significantly affected delivery to brain. Intrathecal administration of @entity3027 , via the cisterna magna, resulted in undetectable concentrations in brain tissue and plasma at 30 and 60 min. However, osmotic blood-brain barrier opening significantly increased @entity3027 delivery to brain after its carotid administration. A maximum concentration of 0.18% per gram of the total administered dose was achieved at 120 min, and the cerebrovascular permeability-surface area was increased to 30.8 x 10(-6) @entity8639 . Intracerebral @entity3027 concentrations did not decline significantly during the 240 min study. Osmotic blood-brain barrier opening increased the area under the brain concentration vs. time curve, measured between 30 and 240 min, from 0.012 x 10(6) U.min/g, in controls, to 1.24 x 10(6) U.min/g, at least 100-fold. This study indicates that osmotic blood-brain barrier opening significantly increases the delivery of @entity3027 into brain, and that delivered remains within the brain for many hours.
