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Diabetes 53:877-881, 2004
© 2004 by the American Diabetes Association, Inc.
Inhalation of Insulin in Dogs
Assessment of Insulin Levels and Comparison to Subcutaneous Injection
1 Vanderbilt University Medical Center, Nashville, Tennessee
2 Lovelace Respiratory Research Institute, Albuquerque, New Mexico
3 Nektar Therapeutics, San Carlos, California
4 Aventis, Bridgewater, New Jersey
5 Pfizer, New York, New York
Pulmonary insulin delivery is being developed as a more acceptable alternative to conventional subcutaneous administration. In 15 healthy Beagle dogs (average weight 9.3 kg), we compared insulin distribution in arterial, deep venous, and hepatic portal circulation. Dogs received 0.36 units/kg s.c. regular human insulin (n = 6) or 1 mg (2.8 units/kg) or 2 mg (5.6 units/kg) dry-powder human inhaled insulin (n = 3 and 6, respectively). Postinhalation of inhaled insulin (1 or 2 mg), arterial insulin levels quickly rose to a maximum of 55 ± 6 or 92 ± 9 µU/ml, respectively, declining to typical fasting levels by 3 h. Portal levels were lower than arterial levels at both doses, while deep venous levels were intermediate to arterial and portal levels. In contrast, subcutaneous insulin was associated with a delayed and lower peak arterial concentration (55 ± 8 µU/ml at 64 min), requiring 6 h to return to baseline. Peak portal levels for subcutaneous insulin were comparable to those for 1 mg and significantly less than those for 2 mg inhaled insulin, although portal area under the curve (AUC) was comparable for the subcutaneous and 2-mg groups. The highest insulin levels with subcutaneous administration were seen in the deep venous circulation. Interestingly, the amount of glucose required for maintaining euglycemia was highest with 2 mg inhaled insulin. We conclude that plasma insulin AUC for the arterial insulin level (muscle) and hepatic sinusoidal insulin level (liver) is comparable for 2 mg inhaled insulin and 0.36 units/kg subcutaneous insulin. In addition, arterial peak concentration following insulin inhalation is two times greater than subcutaneous injection; however, the insulin is present in the circulation for half the time.
Address correspondence and reprint requests to Alan D. Cherrington, MD, Vanderbilt University Medical Center, 704 Medical Research Building 1, Nashville, TN 37131-0615. E-mail: alan.cherrington{at}mcmail.vanderbilt.edu
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