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Determination of free fractions of tricyclic antidepressants

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Summary

The plasma protein binding of amitriptyline, imipramine, clomipramine, and their primary demethylated metabolites were studied by means of a method combining dialysis and gas chromatography. Equilibrium in dialysis of serum containing amitriptyline and its metabolite nortriptyline was attained in about 0.5 h with the drug dissolved in the serum compartment, and in about 2 h with the drug passing from the buffer to the serum compartment.

The calculation of free fractions was influenced by variations with dialysis time in the volumes of serum and buffer. Increase of pH in serum increased the protein binding of the weakly basic drugs studied, and made the Donnan distribution effects more pronounced. At pH 7.4, the Donnan effect was negligible.

Binding parameters for the 6 tricyclic antidepressant substances studied were estimated for the binding to α1-acid glycoprotein and for total binding in serum. For α1-acid glycoprotein, the k-values ranged from 1·105 to 8·105 M−1, and for pooled serum from 0.4·105 to 8·105 M−1. The determined number of binding sites on the α1-acid glycoprotein was, on average 0.87 for the 6 substances. In serum, the binding capacity was 2–14 times the concentration of α1-acid glycoprotein.

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References

  • Bailey NIJ (1959) Statistical methods in biology. Hodder and Stoughton, London

    Google Scholar 

  • Bertilsson L, Braithwaite R, Tybring B, Garle M, Borgå O (1979) Techniques for plasma protein binding of demethylchlomipramine. Clin Pharmacol Ther 266:2:265–271

    Google Scholar 

  • Borgå O, Azarnoff D, Plym Forshell G, Sjöqvist F (1969) Plasma protein binding of tricyclic antidepressants in man. Biochem Pharmacol 18:2135–2143

    Google Scholar 

  • Braithwaite R (1980) Plasma protein binding of tricyclic antidepressants. Postgraduate Med J 56 (Suppl 1):107–111

    Google Scholar 

  • Brinkschulte M, Breyer-Pfaff U (1979) Binding of tricyclic antidepressants and perazine to human plasma. Methodology and findings in normals. Naunyn-Schmiedeberg's Arch Pharmacol 308:1–7

    Google Scholar 

  • Brinkschulte M, Breyer-Pfaff U (1980) The contribution of α1-acid glycoprotein, lipoproteins, and albumin to the plasma binding of perazine, amitriptyline, and nortriptyline in healthy man. Naunyn-Schmiedeberg's Arch Pharmacol 314:61–66

    Google Scholar 

  • Brrun Kristensen C, Gram L (1982) Equilibrium dialysis for determination of protein binding of imipramine — evaluation of a method. Acta Pharmacol Toxicol 50:130–136

    Google Scholar 

  • Bull HB (1964) An introduction to physical biochemistry. FA Davis Company, Philadelphia

    Google Scholar 

  • Burch JE, Roberts SG, Raddats MA (1981) Binding of amitriptyline and nortriptyline in plasma. Psychopharmacology 75: 262–272

    Google Scholar 

  • Harper HA (1969) Review of physiological chemistry. Lange Medical Publications, Los Altos

    Google Scholar 

  • Laurell CB (1972) Electroimmunoassay. Scand J Clin Lab Invest 29 (Suppl 124):21

    Google Scholar 

  • Muller W, Stillbauer A (1983) Characterization of a common binding site for basic drugs on human α1-acid glycoprotein (orosomucoid). Naunyn-Schmiedeberg's Arch Pharmacol 322:170–173

    Google Scholar 

  • Nyberg G, Mårtensson E (1977) Quantitative analysis of tricyclic antidepressants in serum from psychiatric patients. J Chrom 143:491–497

    Google Scholar 

  • Nyberg G, Mårtensson E (1982) Binding of thioridazine and thioridazine metabolites to serum proteins — an in vitro study. Naunyn-Schmiedeberg's Arch Pharmacol 319:189–196

    Google Scholar 

  • Piafsky K, Borgå O (1977) Plasma protein binding of basic drugs. I: Selective displacement from α1-acid glycoprotein by tris-(butoxyethyl)phosphate. II: Improtance of α1-acid glycoprotein for interindividual variation. Clin Pharmacol Ther 22:539–549

    Google Scholar 

  • Vallner JJ, Perrin JH, Wold S (1976) Comparison of graphical and computerized methods for calculation of binding parameters for two strongly bound drugs to human serum albumin. J Pharmacol Sci 65:1182–1187

    Google Scholar 

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Nyberg, G., Mårtensson, E. Determination of free fractions of tricyclic antidepressants. Naunyn-Schmiedeberg's Arch. Pharmacol. 327, 260–265 (1984). https://doi.org/10.1007/BF00502459

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  • DOI: https://doi.org/10.1007/BF00502459

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