Enhanced insulin absorption in the rabbit airways and lung by sodium dioctyl sulfosuccinate.
The objective of this investigation was to study regional absorption of inhaled insulin together with an enhancer (sodium di-octyl-sulfosuccinate [DOSS]) in the rabbit airways and lung. Insulin was administered with or without DOSS by aerosol inhalation, intratracheal infusion, intranasally, sublingually, and without DOSS intravenously. Blood glucose and plasma levels of insulin were measured during 100 min from the start of administration. Inhalation of insulin (3 U) with 0.25% or 1% DOSS decreased average blood glucose levels significantly more than inhalation of insulin (3 U) without DOSS. Intratracheal administration of 1.5 U of insulin with 0.25% DOSS in 0.3 mL of vehicle decreased the average blood glucose level significantly compared with intratracheal administration of 1.5 U of insulin and no DOSS in 0.3 mL of vehicle and compared with 1.5 U of insulin with 0.25% DOSS in 0.15 mL of vehicle. Intravenous insulin (1.5 U) and inhaled (1.5 U) insulin in 0.25% DOSS decreased average blood glucose levels significantly compared with intratracheal (0.15 mL), intranasal, and sublingual administration of 1.5 U of insulin with 0.25% DOSS. The bioavailability of inhaled insulin (1.5 U) with 0.25% DOSS was estimated to be 16% in comparison with 7% for intratracheally (0.15 mL), 1% intranasally, and 0.8% sublingually administered insulin (1.5 U with 0.25% DOSS), respectively. Inhaled insulin together with the absorption enhancer DOSS decreased the blood glucose level more effectively than insulin given intratracheally, intranasally, or sublingually. The effect on blood glucose reflected the difference in plasma insulin concentration for the different routes of administration.
Dahlbäck
Magnus
M
Experimental Medicine, AstraZeneca R&D Lund, Sweden. magnus.dahlback@astrazeneca.com
Eirefelt
Stefan
S
Bäckström
Kjell
K
Larsson
Per
P
Almér
Lars-Olof
LO
Wollmer
Per
P
Jonson
Björn
B
D000042:Absorption; D000280:Administration, Inhalation; D000336:Aerosols; D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D001786:Blood Glucose / Q000032:analysis; D001980:Bronchi / Q000378:metabolism*; D004143:Dioctyl Sulfosuccinic Acid / Q000494:pharmacology*; D007328:Insulin / Q000008:administration & dosage / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D011817:Rabbits
D000336:Aerosols; D001786:Blood Glucose; D007328:Insulin; D004143:Dioctyl Sulfosuccinic Acid