Distribution of amitriptyline and nortriptyline in blood: role of alpha-1-glycoprotein.

Abstract:

:To interpret blood levels of tricyclic antidepressants, we studied the distributions of amitriptyline and nortriptyline in human blood and explored their control by plasma factors. Each compound (300 ng/ml) was added to whole adult blood and to cord blood with decreased alpha-1-glycoprotein (AGP). Drugs (250 ng/ml) were also added to washed erythrocytes (RBCs) resuspended in autologous plasma or saline (hematocrit = 0.4) with or without AGP, albumin, or tris(2-butoxyethyl) phosphate (TBEP), used to displace AGP-bound drugs. Plasma AGP was determined in all adult blood donors (n = 17). With adult blood, plasma amitriptyline was 393 +/- 52 ng/ml, RBC amitriptyline was 184 +/- 33 ng/ml. Plasma and RBC nortriptyline were 199 +/- 28 and 288 +/- 39 ng/ml, respectively. With saline, cellular amitriptyline and nortriptyline were 81 +/- 10 and 88 +/- 6%, respectively. With plasma, cellular amitriptyline and nortriptyline were 25 +/- 8 and 49 +/- 10%, respectively. The corresponding cord blood values were 52 +/- 12 and 62 +/- 6%. Graded increments of AGP in saline reproduced the distribution pattern seen with increasing concentrations of plasma. Albumin did not influence drug distribution. TBEP markedly increased erythrocyte amitriptyline in adult but not in cord blood. Plasma AGP correlated positively (p = 0.031) with the RBC/plasma ratio of amitriptyline. Amitriptyline is predominantly distributed in plasma, nortriptyline in RBCs. This differential distribution is dose dependent and reflects the higher binding of amitriptyline to AGP when compared with nortriptyline. Interpretation of tricyclic antidepressant blood levels is clarified by obtaining assays from RBCs and plasma.

journal_name

Ther Drug Monit

authors

Amitai Y,Kennedy EJ,DeSandre P,Frischer H

doi

10.1097/00007691-199308000-00002

subject

Has Abstract

pub_date

1993-08-01 00:00:00

pages

267-73

issue

4

eissn

0163-4356

issn

1536-3694

journal_volume

15

pub_type

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