Enhancement of intestinal insulin absorption by bile salt-fatty acid mixed micelles in dogs.
The pharmacokinetics and pharmacodynamics of porcine zinc insulin following intravenous (iv), intrajejunal, and ileocolonic delivery were evaluated in dogs. The concentration-time profile of plasma immunoreactive insulin following iv injection could be best described by a two-compartment model with a mean distribution half-life of 1.1 min and a mean elimination half-life of 5.6 min. Maximum hypoglycemia occurred at 15 min after injection. Intrajejunal administration of 10 units/kg insulin in phosphate-buffered saline resulted in minimal insulin absorption or hypoglycemia. Incorporation of mixed micelles containing 30 mM sodium glycocholate and 40 mM linoleic acid significantly improved enteral insulin absorption. When delivered with mixed micelles, the mean absolute bioavailability of insulin was 1.8%. To study the effect of intestinal site on insulin uptake, the same formulation was delivered to the ileocolonic region. The mean absolute bioavailability of insulin absorbed from this site was 0.6%. Delivery of insulin to both sites caused significant hypoglycemia in all dogs. Insulin combined with mixed micelles is enterally absorbed in dogs; however, the bioavailability is much lower than that observed in similar studies with rats.
Scott-Moncrieff
J C
JC
Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Purdue University, West Lafayette, IN 47907.
Shao
Z
Z
Mitra
A K
AK
D000818:Animals; D001647:Bile Acids and Salts / Q000008:administration & dosage / Q000494:pharmacology*; D004285:Dogs; D005227:Fatty Acids / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D007082:Ileum / Q000378:metabolism; D007275:Injections, Intravenous; D007322:Instillation, Drug; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000378:metabolism; D007583:Jejunum / Q000378:metabolism; D008297:Male; D008823:Micelles
D001647:Bile Acids and Salts; D005227:Fatty Acids; D007328:Insulin; D008823:Micelles