FROM SOMATOSTATIN TO SANDOSTATIN(R) - PHARMACODYNAMICS AND PHARMACOKINETICS

Somatostatin (SRIF) and its octapeptide analogue, octreotide (Sandostatin®), have a similar high affinity for specific receptors with 50% inhibitory concentrations (IC50s) in the subnanomolar range. Hence, the striking superiority of octreotide in vivo, which includes duration of action, specificity, and potency, must originate from its different distribution, metabolism, and excretion behavior. In animals and humans, investigations of their pharmacodynamic/pharmacokinetic relationship show plasma levels of 0.2 to 0.5 ng/mL (∼0.3 nmol/L) to be therapeutically relevant for both peptides. The much lower clearance rates and improved metabolic stability in the circulation and in target organs of octreotide, compared with SRIF, result in much longer-lasting, therapeutically relevant plasma and tissue levels and therefore in a longer duration of action. Their apparently specific inhibitory action on growth hormone when compared with that on insulin is pharmacodynamically based, and may be exaggerated by physiological mechanisms of carbohydrate regulation. In summary, there is a distinct relationship between the pharmacokinetic profiles and pharmacodynamic behavior of SRIF and its analogue, Sandostatin®. © 1992.