Improvement of intestinal peptide absorption by a synthetic bile acid derivative, cholylsarcosine.
The potential of the nontoxic bile salt derivative, cholylsarcosine, to enhance the intestinal absorption of peptides was investigated in vitro and in situ. The permeation of the two model peptides octreotide and vasopressin-[arg(8)CT>/=CS, whereas ursodeoxycholic acid exhibited no absorption enhancement. Determination of the cytotoxic potential of the bile salts revealed the same rank order. In rats, octreotide and desmopressin were absorbed from the gastrointestinal-tract with moderate absorption efficiency. Coadministration of bile salts resulted in an increased absorption efficiency. The effect of CS was similar to that of CT. In conclusion, CS shows absorption enhancement properties and a relatively low cytotoxicity. It offers an alternative as absorption enhancer as compared to conventional bile acids which may have a potential cocarcinogenic risk.
Michael
S
S
Institut für Pharmazeutische Technologie und Biopharmazie, Ruprecht-Karls-Universität Heidelberg, Heidelberg, Germany.
Thöle
M
M
Dillmann
R
R
Fahr
A
A
Drewe
J
J
Fricker
G
G
D000818:Animals; D019540:Area Under Curve; D001647:Bile Acids and Salts / Q000494:pharmacology; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002793:Cholic Acids / Q000494:pharmacology*; D003911:Dextrans; D017097:Electric Impedance; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives; D005456:Fluorescent Dyes; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D008567:Membranes, Artificial; D010455:Peptides / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D012521:Sarcosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013268:Stimulation, Chemical
D001647:Bile Acids and Salts; D002793:Cholic Acids; D003911:Dextrans; D005456:Fluorescent Dyes; D008567:Membranes, Artificial; D010455:Peptides; C015219:fluorescein isothiocyanate dextran; D016650:Fluorescein-5-isothiocyanate; C061997:cholylsarcosine; D012521:Sarcosine