Distribution of nortriptyline in human blood: effects of temperature, pH, and drug concentration

An in vitro study of putative factors causing postvenipuncture redistribution of the tricyclic antidepressant nortriptyline (NT) in blood was carried out in blood samples from a single subject. The influence of varying temperature, pH, and drug concentration on the protein binding of NT was assessed by equilibrium dialysis. The influence of the same variables on the distribution of NT in whole blood was measured by calculating the cell/plasma (C/P) drug concentration ratios after centrifugation of blood samples. Variation in temperature did influence the distribution of NT in blood considerably. From 4 to 37 degrees C, the C/P ratio was found to increase from 1.0 +/- 0.1 to 1.7 +/- 0.2, and protein binding expressed as unbound fraction from 2.9 +/- 0.2 to 7.0 +/- 1.1% (mean +/- SD). Neither pH variations within the 7.0-7.6 range, nor variations in drug concentration, were found to alter NT distribution at 37 degrees C. The observed effect of temperature on NT distribution shows that handling of blood samples from patients taking NT should be standardized in order to avoid errors of interpretation.