Oral Administration of Insulin with Chymotrypsin Inhibitors

Abstract

Enteric-coated capsules containing insulin (25 U/kg) and chymotrypsin inhibitor FK-401 (10 to 40 mg/kg) were administered orally to beagle dogs. FK-401 increased the intestinal absorption of insulin dose-dependently. When 40 mg/kg of FK-401 was co-administered with insulin, plasma IRI level reached to 366 μU/ml and plasma glucose fell to 59% compared with the level before. Such an effect was observed when insulin was co-administered with water-soluble chymotrypsin inhibitors FK-317 hydrochloride and FK-448, but was not when water-insoluble or slightly-soluble inhibitors chymostatin or FK-317 maleate was used. Some acids such as citric acid, lactic acid etc. enhanced the effect of chymotrypsin inhibitor on the absorption of insulin.