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Abstract
The binding constants of the binding between thioridazine and its metabolites, side-chain sulfoxide, side-chain sulfone and ring sulfoxide, on the one hand, and the plasma proteins, alpha 1-acid glycoprotein, albumin and total serum proteins, on the other, were determined. The binding constants between the drug substances and alpha 1-acid glycoprotein were found to be about a thousand times higher than the binding constants between the drug substances and albumin. The binding constants of whole serum were close to those of alpha 1-acid glycoprotein. Analysis of the binding data indicated competition between thioridazine and its metabolites. A number of drug substances were screened for possible binding interaction with thioridazine and its metabolites. Tricyclic antidepressants and propranolol significantly increased the free concentration of thioridazine. Also salicyclic acid and the plasticizing agent, TBEP, had this effect.
Published Version
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