From somatostatin to Sandostatin: pharmacodynamics and pharmacokinetics.
Somatostatin and its octapeptide analogue octreotide (Sandostatin) have a similar high affinity for specific receptors with IC50s in the sub-nanomolar 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 behaviour. In animals and humans, investigations on their pharmacodynamic/pharmacokinetic relationship show plasma levels of 0.2-0.5 ng/ml (approximately 0.3 nM) to be therapeutically relevant for both peptides. The much lower clearance and improved metabolic stability in the circulation and in target organs of octreotide compared with somatostatin, result in much longer lasting, therapeutically relevant plasma and tissue levels and therefore in a longer duration of action. Their apparently specific inhibitory action of 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 pharmacokinetic profiles and pharmacodynamic behaviour of somatostatin and its analogue Sandostatin.
Marbach
P
P
Preclinical Department, Sandoz Pharma Ltd., Basel, Switzerland.
Briner
U
U
Lemaire
M
M
Schweitzer
A
A
Terasaki
T
T
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D006801:Humans; D015282:Octreotide / Q000493:pharmacokinetics* / Q000494:pharmacology*; D013004:Somatostatin / Q000493:pharmacokinetics* / Q000494:pharmacology*; D014018:Tissue Distribution
D013004:Somatostatin; D015282:Octreotide