PHARMACOKINETIC, METABOLIC, AND ANTIDIARRHEAL PROPERTIES OF (D AND L)HEPTAPEPTIDES OF SORBIN IN RODENT

The C-terminal heptapeptide-amide (C7-sorbin) is the minimal biologica lly active fragment of sorbin inducing an increase in intestinal hydro electrolytic 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-sorb in 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, a nd MRT were 34 and 18 min. After SC administration, C-max attained 0.4 1% and 0.12% of the dose/ml, respectively. The IP route showed a 45-mi n delay before C-max and a 100% bioavailability for both peptides. D7- sorbin was principally excreted in urine, as shown by balance study, a nd in part in intact form, as controlled by mass spectrometry. D7-sorb in induced a significant decrease of the VIP-induced ileal secretion, previously observed with C7-sorbin. The change of L-Ala to D-Ala incre ased the stability of the synthetic C-terminal peptide of sorbin where as its biological activity, bioavailability, and route of elimination were unchanged.