Somatostatin analogs with improved oral bioavailability.
Cyclic hexapeptide analogs of somatostatin with insulin, glucagon, and growth hormone (GH) release inhibitory potencies of 50-200 times those of somatostatin have been synthesized. Replacement of the Phe-7 residue with histidine has resulted in increased oral bioavailability and duration of action. Metabolic degradation of L-Trp containing analogs upon oral administration has also been overcome by incorporation of histidine. The all L-amino acid containing analog cyclo(NMePhe-His-Trp-Lys-Val-Ala) shows oral bioavailability comparable to D-Trp containing analogs.
D000284:Administration, Oral; D000595:Amino Acid Sequence; D000818:Animals; D001682:Biological Availability; D005934:Glucagon / Q000378:metabolism; D006728:Hormones / Q000138:chemical synthesis / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D010456:Peptides, Cyclic / Q000138:chemical synthesis; D051381:Rats; D012636:Secretory Rate / Q000187:drug effects; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship
D006728:Hormones; D007328:Insulin; D010456:Peptides, Cyclic; D013004:Somatostatin; D005934:Glucagon