Estimation of blood levels of endothelin and neurokinin receptor antagonists at the rat portal and jugular veins after oral administration as a tool in peptide drug design.
The blood concentration of three representative endothelin and four neurokinin receptor antagonists were monitored both at the portal and jugular vein of rats 30, 60 and 90 min after oral administration. Peptide-derived structures, in the size range tetra-pentapeptides, were shown to be absorbed in the reverse order of their log P values, to be weakly metabolized in the first hepatic transit and to maintain high blood levels during the observation time. These interesting results obtained by a simple and convenient UV assay, stress once again the importance of monitoring oral absorption early in the process of peptide drug design.
Paladino
J
J
Departments of Peptide Chemistry, Clinical Biology and Analytical Chemistry, Institut de Recherches SERVIER, France.
Kucharczyk
N
N
Morris
A D
AD
Thibault-Naze
M
M
Mahieu
J P
JP
Serkiz
B
B
Volland
J P
JP
Autissier
C
C
Fauchere
J L
JL
D000042:Absorption; D000284:Administration, Oral; D000818:Animals; D015195:Drug Design; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000097:blood* / Q000737:chemistry* / Q000494:pharmacology; D007601:Jugular Veins / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D011169:Portal Vein / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017466:Receptors, Endothelin / Q000097:blood; D018040:Receptors, Neurokinin-1 / Q000097:blood; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors / Q000097:blood; D018042:Receptors, Neurokinin-3 / Q000037:antagonists & inhibitors / Q000097:blood; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors* / Q000097:blood
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D064729:Neurokinin-1 Receptor Antagonists; D017466:Receptors, Endothelin; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; D018039:Receptors, Tachykinin