Binding interaction of polystyrene sulfonate and amitriptyline

The resin polystyrene sulfonate is often used for binding potassium for prevention of hyperkalaemia. Because of their binding properties, resins could potentially bind other medications before they can be absorbed completely and thereby decrease their bioavailability. This is confirmed in in vitro binding interaction studies. Our own in vitro research has shown a binding interaction between polystyrene sulfonate and amitriptyline.
More information is needed on this possible binding interaction to use amitriptyline and polystyrene sulfonate effectively and safely.
The objective is to determine the effect of the binding interaction, that was found in vitro, on drug exposure in healthy volunteers when amitriptyline and polystyrene sulfonate are used simultaneously.
The study design is a prospective, cross-over trial in healthy volunteers.
Main study parameter: Difference in exposure of amitriptyline in the presence and absence of polystyrene sulfonate, expressed in Cmax and AUC0-8h.
The participants will visit the hospital twice. Both times they will receive a single dose of amitriptyline and once they will receive polystyrene sulfonate concomitantly. Six blood samples will be collected, taken from a peripheral intravenous catheter, at each visit.

Polystyrene sulfonate shows an in-vitro binding interaction with amitriptyline, causing 70-80% binding of amitriptyline to polystyrene sulfonate. The hypothesis is that polystyrene sulfonate binds to amitriptyline when taken simoultaneously in healthy volunteers, leading to decreased exposure to amitriptyline.

After intake of amitriptyline with/without polystyrene sulfonate

Intake of amitriptyline alone and amitriptyline with polysytrene sulfonate