Radioimmunoassay for Doxepin and Desmethyldoxepin

Abstract

Ahs1racr:A simple and sensitive radioimmunoassay (RIA) for the determination of doxepin and desmethyldoxepin in plasma or serum has been developed using a previously reported antiserum to the tricyclic antidepressants. Before assay, doxepin is separated from desmethyldoxepin with selective extraction at different pH values enabling each to be measured specifically. 'H-imipramine is used as tracer. By using the extraction procedure doxepin and desmethyldoxepin concentrations can be measured down to 9 nmol/l from a 0.1 rnl sample. If necessary, sensitivity can be doubled by taking a 0.2 ml sample to the extraction. Recoveries of doxepin and desmethyldoxepin were quantitative when the drugs were added at different concentrations to normal, pooled human plasma and the inter-and intra-assay coefficients of variation did not exceed 9%. The concentrations obtained from patient samples by the present RIA correlated well with those by high-pressure liquid chromatography. The RIA was also shown to be useful in pharmacokinetic single dose studies with doxepin.

Single Dose Pharmacokinetics of Doxepin in Healthy Volunteers

“…In the present study a mean first-pass metabolism of 71% was estimated, which is in agreement with the mean value of 73% in the study of Ziegler et al (1978a). Thus, when assuming an equal absorption, the first-pass metabolism of DOX appears to be somewhat more extensive than those observed with nortriptyline (35% by Alexanderson et al 1973, and34% by Alvan et al 1977), amitriptyline (60% by Ziegler et al 1978b), and imipramine (53% by Gram & Christiansen 1975).…”

“…The absorption was rapid (Cmu was observed at 1-2 hours) and the disappearance thereafter biphasic with a mean distribution half-life of 2.1 hours and elimination half-life of 17.9 hours. Ziegler et al (1978a) do not give a value for ty2 in their report, but the mean elimination half-life (16.8 hours) is similar to ours.…”

“…In this study equilibrium dialysis gave a mean binding of 75.5% for DOX and 76.0% for DDOX, which values are lower than those reported for other tricyclic antidepressants. In our laboratory, for instance, the mean protein binding of nortriptyline was 86.0% in serum of seven volunteers in a study in which the same assay technique was used (Virtanen 1980). In the study of BorgA et al (1969) the binding of amitriptyline, nortriptyline, imipramine, desipramine, and protriptyline was estimated (by ultrafiltration) to be generally over 90%.…”

“…The protein binding of DOX and DDOX was measured by equilibrium dialysis as described earlier (Virtanen 1980). The 2and 6-hour serum samples were used.…”

“…The aim of the present work was to study the pharmacokinetics of DOX after an oral dose by measuring the serum, plasma and red blood cell concentrations of DOX and its active metabolite, desmethyldoxepin (DDOX), by a new radioimmunoassay (Virtanen et a/. 1980).…”