Medications> Glucose-lowering>

INDICATIONS

• There are no insulin preparations currently approved for other than subcutaneous or intravenous administration.

• Only in research studies.

MECHANISM

• Inhaled insulin is absorbed across the alveolar membrane.
• Microsphere encapsulation has been developed to enhance absorption (Technosphere^®).
• Animal and limited human studies have demonstrated oral, nasal and rectal absorption of insulin when bound to certain carriers such as bile acids or when encapsulated.
• Extensive experience in human trials of implanted insulin infusion pumps.

PHARMACOKINETIC

COMMENTS

• The FDA approval and commercial launching of inhaled insulin, Exubera®, in September, 2006 followed extensive pre-clinical trials demonstrating efficacy.
• The main side effect of inhaled insulin was a small decrease in pulmonary function, specifically FEV1.
• The delivery device was cumbersome, insulin was delivered in mg rather than unit doses, and regular pulmonary function tests were required.
• For these reasons, the company, Pfizer, decided in October, 2007, to stop production, and it is no longer available.
• Subsequently, in April, 2008, the FDA issued a letter noting a possible association of Exubera® with lung cancer: of 4740 patients on Exubera®, 6 developed lung cancer, vs. 1 of 4,292 on placebo.
• Mannkind, Inc. developed a microencapsulation technique (Technoshpere®), and submitted a new drug application to the FDA in March, 2009.
• Other insulin delivery routes (particularly oral and encapsulated preparations for GI absorption) are in earlier stages of development.
• Implanted insulin infusion pumps have been used for up to 20 years, in over 400 humans, the majority in France.
• Manufacturer is not currently proceeding with FDA application for market approval in the U.S., although approval has been granted in France.

REFERENCES