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Alpha 1-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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No abstract

Conflicting results on the correlation of tricyclic levels in plasma and saliva have raised doubts about the clinical usefulness of monitoring these drugs in the latter body fluid. However, saliva drug levels may reflect the free plasma concentration, which possibly determines its level in the brain. In two groups of depressive patients, the evolution was studied of the levels of amitriptyline and nortriptyline in plasma (as free and total) and in saliva, after the administration of amitriptyline. The results show a poor correlation between total plasma and saliva concentration of amitriptyline and nortriptyline, respectively. Levels of both tricyclics in saliva exceed by far those measured in plasma dialysate. However, the relationship is such that free plasma concentrations may be predicted from those measured in saliva, if one takes into account saliva pH at the moment of collecting the sample.