ISSN:
1432-1912
Keywords:
Amitriptyline
;
Imipramine
;
Clomipramine
;
Demethylated metabolites
;
Free fractions
;
Serum
;
Equilibrium dialysis
;
Gas chromatography
;
Binding parameters
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00502459
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