In this article, we will discuss Pasireotide (Mechanism of Action). So, let’s get started.
Mechanism of Action
Pasireotide is an injectable cyclohexapeptide somatostatin analogue. Pasireotide exerts its
pharmacological activity via binding to somatostatin receptors (ssts). Five human somatostatin receptor subtypes are known: hsst 1, 2, 3, 4, and 5. These receptor subtypes are expressed in different tissues under normal physiological conditions. Corticotroph tumor cells from Cushing’s disease patients frequently over-express hsst5 whereas the other receptor subtypes are often not expressed or are expressed at lower levels. Pasireotide binds and activates the hsst receptors resulting in inhibition of ACTH secretion, which leads to decreased cortisol secretion.
Pharmacodynamics
Cardiac Electrophysiology
QTcI interval was evaluated in a randomized, blinded, crossover study in healthy subjects investigating pasireotide doses of 0.6 mg b.i.d. and 1.95 mg b.i.d. The maximum mean (95% upper confidence bound) placebo-subtracted QTcI change from baseline was 12.7 (14.7) ms and 16.6 (18.6) ms, respectively. Both
pasireotide doses decreased heart rate, with a maximum mean (95% lower confidence bound) placebo-subtracted change from baseline of -10.9 (-11.9) beats per minute (bpm) observed at 1.5 hours for pasireotide 0.6 mg bid, and -15.2 (-16.5) bpm at 0.5 hours for pasireotide 1.95 mg b.i.d. The supratherapeutic dose (1.95 mg b.i.d) produced mean steady-state Cmax values 3.3-fold the mean Cmax for the 0.6 mg b.i.d dose in the study.