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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Blood-brain barrier transfer and cerebral uptake of antiepileptic drugs.

The permeability across the blood-brain barrier of phenobarbital, phenytoin, clonazepam, and diazepam was determined in a total of 29 patients with the double-indicator dilution method. Cerebral blood flow was measured with the 133Xe intra-arterial injection method. The unidirectional extraction (E) of the four drugs was 0.07, 0.11, 0.42, and 0.42, respectively. Permeability surface area products (PS) calculated for the drugs depended on E as well as on the plasma protein binding of the drugs and the cerebral blood flow and was calculated as 0.1, 0.5, 0.5, and 2.6 ml gm-1 min-1, respectively. A mathematic model of cerebral uptake and concentration is presented. The brain concentration of each drug is then calculated for two different states, one with a sudden rise from zero to an arterial concentration, which remains constant, and the other with the arterial concentration, which is achieved after rapid intravenous injection. The cerebral uptake rate of clonazepam and diazepam was much more rapid than that of phenobarbital and phenytoin. After intravenous clonazepam or diazepam injection, half-maximal gray matter concentration is reached about 15 sec after the drug arrives at the brain.[1]


  1. Blood-brain barrier transfer and cerebral uptake of antiepileptic drugs. Paulson, O.B., Györy, A., Hertz, M.M. Clin. Pharmacol. Ther. (1982) [Pubmed]
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