FROM SOMATOSTATIN TO SANDOSTATIN(R) - PHARMACODYNAMICS AND PHARMACOKINETICS

Somatostatin and its octapeptide analogue octreotide (Sandostatin(R)) have a similar high affinity for specific receptors with IC50, in the sub-nanomolar range. Hence, the striking superiority of octreotide in vivo, which includes duration of action, specificity, and potency, mus t originate from its different distribution, metabolism, and excretion behaviour. In animals and humans, investigations on their pharmacodyn amic/pharmacokinetic relationship show plasma levels of 0.2-0.5 ng/ml (approximately 0.3 nM) to be therapeutically relevant for both peptide s. The much lower clearance and improved metabolic stability in the ci rculation and in target organs of octreotide compared with somatostati n, result in much longer lasting, therapeutically relevant plasma and tissue levels and therefore in a longer duration of action. Their appa rently specific inhibitory action of growth hormone when compared with that on insulin is pharmacodynamically based and may be exaggerated b y physiological mechanisms of carbohydrate regulation. In summary, the re is a distinct relationship between pharmacokinetic profiles and pha rmacodynamic behaviour of somatostatin and its analogue Sandostatin(R) .