Serum concentration and protein binding of thioridazine and its metabolites in patients with chronic alcoholism.
The blood chemistry and clinical pharmacokinetics of thioridazine and its metabolites, side-chain sulphoxide, side-chain sulphone and ring sulphoxide, were studied in 31 alcoholics and were compared with values in 17 thioridazine-treated controls without alcoholism. Pathological blood chemistry values, including abnormal liver function and protein concentrations, were common among the alcoholics. In relation to dosage, the majority had a low serum concentration of thioridazine and at a given concentration of thioridazine they had high serum concentrations of its metabolites. Positive intercorrelations were found between pathological liver function tests, prolonged serum half-life and increased serum concentration of thioridazine. The free fractions of thioridazine, side-chain sulphoxide and ring sulphoxide were significantly higher and those of the side-chain sulphone lower in the alcoholics than in the controls. The free fractions of side-chain and ring sulphoxide were significantly increased in patients with a low concentration of alpha 1-acid glycoprotein.
D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000097:blood*; D001711:Biotransformation; D001798:Blood Proteins / Q000378:metabolism; D005260:Female; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009961:Orosomucoid / Q000378:metabolism; D011485:Protein Binding; D013450:Sulfones / Q000097:blood; D013454:Sulfoxides / Q000097:blood; D013881:Thioridazine / Q000097:blood*
D001798:Blood Proteins; D009961:Orosomucoid; D013450:Sulfones; D013454:Sulfoxides; D013881:Thioridazine