Phenytoin, phospholipids, and calcium

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Abstract
Binding of phenytoin to phospholipids was found to be related to fatty acid composition. Dipalmitoyl and dioleoyl lecithins, the most abundant lecithins in brain, showed the greatest binding activity. There was an exact correlation between binding activity and phosphorous content in lipids derived from fractionation of total lipids of rabbit and human brain. Phenobarbital showed little interaction with phospholipids. Phospholipid binding of 45Ca++ could be increased up to five times by the addition of 1 ± 10−4 M phenytoin. This enhancement of Ca++-binding may explain the effectiveness of phenytoins in the treatment of hypocalcemic symptoms. Ca++ and phospholipid binding may be important factors in the stabilizing action of phenytoin.