Uptake and/or binding of tricyclic antidepressants in human red cells.

The factors affecting the red blood cells (RBC) uptake and/or binding of tricyclic antidepressants imipramine (IMI) and desmethylimipramine (DMI) were investigated under in vitro conditions. The time course of drug distribution indicated that equilibrium between RBC and medium is reached rapidly. The uptake and/or binding of IMI and DMI to RBC was not saturable and RBC/medium ratio was unaffected by pH, nature of monovalent cations or by the presence of therapeutic concentrations (5-50 ng/ml) of antipsychotic drugs. In the protein-free medium, RBC/medium ratio of DMI was X +/- SE = 2.58 +/- 0.08 (n = 5) and that of IMI was 7.38 +/- 0.12 (n = 6). However, RBC/plasma ratio of DMI was 0.78 +/- 0.04 (n = 7) and IMI ratio was 0.64 +/- 0.03 (n = 9). The RBC/medium ratio was linearly related to free fraction of IMI in a buffer containing 60 mg/ml of human serum albumin with various concentrations of alpha 1-acid glycoprotein (r = 0.971, n = 7). These results suggest that in the absence of proteins the lipid solubility of antidepressants is the main determinant factor in RBC uptake and/or binding, whereas, in the presence of proteins, free fraction of the drug plays the major role. Hence, the RBC/plasma ratio of antidepressants may correlate with treatment outcome in clinical studies better than total drug concentration in plasma.