Protein Binding of Doxepin and Desmethyldoxepin

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Abstract
The protein binding of doxepin (DOX) and desmethyldoxepin (DDOX) [tricyclic antidepressants] were studied in serum and plasma samples from healthy volunteers and psychiatric patients. Binding was measured by equilibrium dialysis (16 h at 37.degree.) and drug concentrations by radioimmunoassay. Albumin and .alpha.1-acid glycoprotein concentrations of the samples were measured by radial immunodiffusion. The mean percentages of unbound DOX were 20.4 .+-. 1.2 and 15.9 .+-. 1.2 in healthy subjects (n = 16) and patients (n = 15), respectively, and those of DDOX, 21.4 .+-. 0.9 and 19.0 .+-. 1.4, respectively. There was a significant negative correlation between serum .alpha.1-acid glycoprotein concentration and free fraction of DOX in both groups. In healthy subjects, a significant negative correlation was also found between albumin concentrations and free fraction of both DOX and DDOX. Binding experiments with isolated protein fractions revealed that all of the total binding in plasma could be explained by binding to albumin and .alpha.1-acid glycoprotein. The observed 2- to 4-fold interindividual variability in the free fractions of these drugs is probably less important than the much larger variability in the total serum concentrations.