Characteristics of plasma protein binding of tacrine hydrochloride: a new drug for Alzheimer's disease.

The aim of this study was to characterise the plasma protein binding of tacrine hydrochloride (THA) in vitro. Binding was assessed in the plasma of 11 healthy individuals aged 20 to 27 years using ultrafiltration followed by HPLC assay. At THA concentrations from 10 to 100 ng/ml protein binding ranged from 78.6 to 71.0%. Binding to commercially available human albumin ranged from 41.7 to 38.3% and to human alpha 1-acid glycoprotein from 23.1 to 12.4% over the THA concentrations from 25 to 100 ng/ml. THA binding and total plasma protein, plasma albumin and alpha 1-acid glycoprotein were measured in healthy young subjects (n = 13), healthy elderly individuals (n = 12) and patients hospitalised with acute illnesses (n = 8). There were significant differences between the groups in total plasma protein, plasma albumin and in alpha 1-acid glycoprotein but no differences in the protein binding of THA which remained constant at about 75%. There was no correlation between THA binding and any plasma protein concentration. The THA binding was not high enough to be of major significance clinically or to reduce the validity of total plasma THA measurement in therapeutic monitoring.