Pharmacokinetic, metabolic, and antidiarrheal properties of (D and L) heptapeptides of sorbin in rodent.
The C-terminal heptapeptide-amide (C7-sorbin) is the minimal biologically active fragment of sorbin inducing an increase in intestinal hydroelectrolytic absorption. An analogue (D7-sorbin), characterized by the replacement of the ultimate C-terminal amino acid L-alanine-amide by D-alanine-amide, was synthetized. For pharmacokinetic studies, D7-sorbin and C7-sorbin were tritium labeled. After IV injection, clearances were 10.6 and 30.2 ml-1 for D7-sorbin and C7-sorbin, respectively, and MRT were 34 and 18 min. After SC administration, Cmax attained 0.41% and 0.12% of the dose/ml, respectively. The IP route showed a 45-min delay before Cmax and a 100% bioavailability for both peptides. D7-sorbin was principally excreted in urine, as shown by balance study, and in part in intact form, as controlled by mass spectrometry. D7-sorbin induced a significant decrease of the VIP-induced ileal secretion, previously observed with C7-sorbin. The change of L-Ala to D-Ala increased the stability of the synthetic C-terminal peptide of sorbin whereas its biological activity, bioavailability, and route of elimination were unchanged.
Nicol
P
P
INSERM Unité 45, Hôpital Edouard Herriot, Lyon, France.
Vienet
R
R
Jourdan
G
G
Dumas
C
C
Abou el Fadil
F
F
Benech
H
H
Grognet
J M
JM
Tarrade
T
T
Pansu
D
D
Descroix-Vagne
M
M
D000818:Animals; D000930:Antidiarrheals / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D001345:Autoradiography; D001682:Biological Availability; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D010446:Peptide Fragments / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D010455:Peptides / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D013552:Swine; D014018:Tissue Distribution
D000930:Antidiarrheals; D010446:Peptide Fragments; D010455:Peptides; C071218:sorbin peptide