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Interindividual differences in the binding of antidepressives to plasma proteins: the role of the variants of alpha1-acid glycoprotein

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Alpha1-acid glycoprotein (AAG) is one of the plasma proteins that bind basic drugs, like amitriptyline (AT) and its metabolite nortriptyline (NT). Two types of genetic polymorphism have been described for AAG: polymorphic forms which, on electrophoresis of the native protein, give four patterns with 5, 6, 7 or 8 bands, and the variants which on by electrophoresis of the desialysed protein, give three patterns with 2 bands, FF, FS and SS. In 31 depressive patients, treated daily with 150 mg AT for 3 weeks, free and total plasma AT and NT were determined, as well as the AAG polymorphic forms and variants. There was only a weak negative correlation between the free fractions of AT and NT and total plasma AAG, but free AT and NT were strongly correlated with the S form (but not the F form) of AAG variants. The differences in binding might be the expression of a further genetic factor determining the steady-state plasma levels of tricyclic drugs.

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Tinguely, D., Baumann, P., Conti, M. et al. Interindividual differences in the binding of antidepressives to plasma proteins: the role of the variants of alpha1-acid glycoprotein. Eur J Clin Pharmacol 27, 661–666 (1985). https://doi.org/10.1007/BF00547045

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Key words

  • amitriptyline
  • drug plasma binding
  • alpha1-acid glycoprotein
  • nortriptyline
  • polymorphic forms
  • protein variants
  • genetic factor
  • depression