Pharmacokinetic, metabolic, and antidiarrheal properties of (D and L) heptapeptides of sorbin in rodent.

Abstract 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, C max attained 0.41% and 0.12% of the dose/ml, respectively. The IP route showed a 45-min delay before C max 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.