Summary
The binding constants of the binding between thioridazine and its metabolites, side-chain sulfoxide, sidechain sulfone and ring sulfoxide, on the one hand, and the plasma proteins, α1-acid glycoprotein, albumin and total serum proteins, on the other, were determined. The binding constants between the drug substances and α1-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 α1-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.
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References
Axelsson R, Mårtensson E, Alling C (1982) Serum concentrations and protein binding of thioridazine and its metabolites in patients with chronic alcoholism. Eur J Clin Pharmacol (in press)
Basett RC, Wright AA, Gross EM, Hine CM (1978) Human tissue distribution of thioridazine during therapy and after poisoning. J Anal Toxicol 2:41–43
Nyberg G, Axelsson R, Mårtensson E (1978) Binding of thioridazine and thioridazine metabolites to serum proteins in psychiatric patients. Eur J Clin Pharmacol 14:341–350
Nyberg G, Axelsson R, Mårtensson E (1981) Cerebrospinal fluid concentrations of thioridazine and its main metabolites in psychiatric patients. Eur J Clin Pharmacol 19:139–148
Piafsky K, Borgå O (1977a) Plasma protein binding of basic drugs (I): Selective displacement from α1-acid glycoprotein by tris-(butoxyethyl)phosphate. Clin Pharmacol Ther 22:539–544
Piafsky K, Borgå O (1977b) Plasma protein binding of basic drugs (II): Importance of α1-acid glycoprotein for interindividual variation. Clin Pharmacol Ther 22:545–549
Scatchard G (1949) The attraction of proteins for small molecules and ions. Ann NY Sci 51:660–672
Vallner J (1977) Binding of drugs by albumin and plasma protein (review). J Pharmacol Sci 66:447–465
Veronese FM, Bevilacqua R, Chaiken IM (1978) Drug-protein interactions: evaluation of the binding of antipsychotic drugs to glutamate-dehydrogenase by quantitative affinity chromatography. Mol Pharmacol 15:313–321
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Nyberg, G., Mårtensson, E. Binding of thioridazine and thioridazine metabolites to serum proteins. Naunyn-Schmiedeberg's Arch. Pharmacol. 319, 189–196 (1982). https://doi.org/10.1007/BF00495864
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DOI: https://doi.org/10.1007/BF00495864