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Com­pound Accumulation

Long per­fu­sion of the com­pound in iso­lated Lan­gen­dorff per­fused hearts (2h)

Time depen­dent vari­a­tion of left ven­tric­u­lar pres­sure and ECG para­me­ters

Cal­cu­la­tion of phar­ma­co­ki­netic para­me­ters of accu­mu­la­tion using time-​dependent for­mu­la­tion of the com­pound at the heart outflow

Amitripty­line: myocar­dial accu­mu­la­tion observed

Pro­gres­sive increase in QTc inter­val dur­ing the 120 min of perfusion

SX: no accu­mu­la­tion observed

Fast increase in QTc inter­val, sta­ble after 20 min of perfusion

accumulation