This document presents information on inhaled insulin as a new method of drug delivery for treating diabetes. It discusses the role of insulin, inhaled insulin devices, the pharmacology and pharmacokinetics of inhaled insulin, its effects on blood glucose levels, equivalent dosing compared to other insulins, and its use in treating type 1 and type 2 diabetes. Adverse effects are noted to include the potential for hypoglycemia, weight gain, and pulmonary issues. Inhaled insulin may provide benefits over injected insulin such as improved patient satisfaction and convenience.

1. INSULIN THROUGH INHALATION
.
OMEGA COLLEGE OF PHARMACY 1
A Concise Presentation
By
Mr. Deepak Sarangi M.Pharm.

2. CONTENTS
 Introduction
 Role of insulin
 Inhaled insulin devices
 Pharmacology of inhaled insulin
 Pharmacokinetics of inhaled insulin
 Glucodynamics of inhaled insulin
 Equivalence dosing of inhaled insulin
 Treatment of diabetes
 Special population
 Adverse effects
 Conclusion
 References
2OMEGA COLLEGE OF PHARMACY

3. INTRODUCTION
Exubera is the name of first formation of inhalable insulin to
receive the USFDA approval. Insulin is traditionally prescribed in
international units(IU), but exubera is prescribed in milligrams(mg). 1mg
of erubera is equivalent to 3IU of INH insulin. Inhalable insulin was
available from sep 2006 to oct 2007 in the market of united states for the
treatment of diabetes as a new method of drug delivery system for
insulin.
Inhaled insulin is a powder from of recombinant human insulin(
rDNA ) formation that has been approved for pulmonary route of
administration in both type-1&2 DM.
3OMEGA COLLEGE OF PHARMACY

4. ROLE OF INSULIN
 Insulin is a polypeptide hormone(MW-6000Da) secreted by the Islets
of langerhans & functioning in the metabolism of carbohydrates &
fats, especially the conversion of glucose to glycogen, which lower
the blood glucose level.
 Insulin consist of 2 chains (alpha & beta) linked by three disulfide
bonds.
 Inhaled insulin is a powered form of recombinant human insulin.
Inhaler is used to deliver the insulin into the lungs where it is
absorbed. Insulin has also helpful for the patients with breast cancer.
4OMEGA COLLEGE OF PHARMACY

5. INHALED INSULIN DEVICES
 The bioavailability of inhaled insulin for each of the devices varies,
but is in the range of 10% to 46% with much of the drug being lost
with in the device.
 Exubera was developed through a collaboration between Nektan
therapeutics and Pfizer was approved by the FDA European
Medicines Agency(EMEA) for treatment of both T1DM & T2DM.
 The insulin delivered by this device is a dry powder formation
packaged in blister packets containing 1mg or 3mg of regular human
insulin.
5OMEGA COLLEGE OF PHARMACY

6. OMEGA COLLEGE OF PHARMACY 6

7. PHARMACOLOGY OF INHALED
INSULIN
 Pharmacology of inhaled insulin involves both the study of
pharmacokinetics & pharmacodynamics.
 β-cell secretion of insulin with rapid onset of action followed
by sustained activity over a period of 2-3hrs control rising
glucose concentration.
 Different inhaled delivery systems to regular insulin
administered subcutaneously which has a peak effect on 30-
60mins after administration & duration of action up to 4hrs.
7OMEGA COLLEGE OF PHARMACY

8. PHARMACOKINETICS OF INHALED
INSULIN
 Pharmacokinetic parameters for various inhaled devices is provided by Patton
et al.
 In a comparison of exubera and regular insulin in healthy nonsmoking males, the
total insulin exposure was similar for inhaled insulin and regular insulin.
 However, the time to maximal insulin concentration was more rapid for inhaled
insulin vs regular insulin.
 In healthy volunteers comparing 3 different technosphere inhaled insulin doses
and regular insulin, similar results were found.
 The AERx system in patients with T1DM revealed there was more rapid rise in
serum insulin in the inhaled group vs regular insulin group.
8OMEGA COLLEGE OF PHARMACY

9. Contd…
 The intrasubject variability to total insulin exposure was 26%
for the inhaled group, indicating that consistent inhalation
techniques could pay a significant role in diabetes control.
 Rave et al compared technosphere insulin to regular insulin in
16 patients with T2DM.
 The total insulin exposure for inhaled insulin was comparable
to that of subcutaneous insulin, the exposure time was shorter
with inhaled insulin, suggesting that the risk of delayed
hypoglycemia may be less with the inhaled insulin formulation.
9OMEGA COLLEGE OF PHARMACY

10. GLUCODYNAMICS OF INHALED INSULIN
 Glucodynamics is measured by determining the infusion rate of glucose
necessary to maintain euglycemia.
 Glucodynamics parameter determines the hypoglycemic effect of therapy.
 In healthy males receiving inhaled insulin, rates of glucose infusion were higher
in the first hour after dosing than in those receiving regular insulin by injection,
correlating with the more rapid rise in serum insulin levels.
 Total glucose consumption was comparable for bioequivalent doses of inhaled
vs regular insulin.
 In individuals with T1DM, the glucose infusion rate profile showed an early
peak rate with inhaled insulin vs regular insulin with a similar glucose
consumption.
10OMEGA COLLEGE OF PHARMACY

11. Contd…
 Rave et al performed mixed meal tolerance tests in 16 individuals
with T2DM and compared the ability of technosphere insulin and
regular insulin to control postprandial glucose levels.
 Both maximal postprandial glucose area under the curve indicating
that for similar insulin exposure, glycemic control was improved
with inhaled insulin.
 After administration, makes inhaled insulin a good candidate for
control of meal-time glucose levels.
11OMEGA COLLEGE OF PHARMACY

12. EQUIVALENCE DOSING OF INHALED INSULIN
 Pharmacokinetic and glucodynamic studies have been performed to
determine the equivalence of each inhaled insulin formulation
relative to subcutaneous insulin.
 In order for patients to receive the appropriate amount of insulin to
cover carbohydrate ingestion, they must perform a series of
inhalations using the doses available for each delivery system.
 For example, a patient normally requiring 10 units of regular insulin
could inhale either three 1mg blisters (9 unit equivalents) or 1mg
blister and 3mg blister (11 unit equivalents) of Exubera to achieve a
comparable insulin dose.
12OMEGA COLLEGE OF PHARMACY

13. TREATMENT OF DIABETES
 The major goal in treating diabetes is to minimize any elevation of
blood sugar (glucose) without causing abnormally low levels of
blood sugar.
 Type 1 diabetes is treated with insulin, exercise, and a diabetic diet.
 Type 2 diabetes is treated first with weight reduction, a diabetic diet,
and exercise.
 When these measures fail to control the elevated blood sugars, oral
medications are used. If oral medications are still insufficient,
treatment with insulin is considered.
13OMEGA COLLEGE OF PHARMACY

14. TYPE 1 DIABETES
 Current strategies to control blood glucose levels in individuals with T1DM
involve subcutaneous insulin injections given multiple times per day ( 2 to 5 ) or
insulin pump therapy via CSII.
 In patients receiving injection therapy, they generally receive long-acting (basal)
insulin 1 or 2 times/day and short–acting insulin with meals to cover post-
prandial meal excursions.
 Multiple daily injection therapy places a burden on patients and is a significant
barrier to optimizing adherence to diabetes regimens aimed at improving
glycemic control.
 Inhaled insulin has the potential replace short-acting insulin analogs, eliminating
as many as 4 injections per day.
14OMEGA COLLEGE OF PHARMACY

15. TYPE 2 DIABETES
 Individuals with T2DM often have complicated medication regimens when
the addition of insulin is considered.
 Patients may be taking several different classes of drugs in an effort to
control blood sugars – oral hypoglycemic agents and insulin sensitizers.
 Rosenstock et al performed a trial in T2DM patients on dual oral agent
therapy who continued to have poor glycemic control.
 Patients were randomized to continued oral therapy, oral therapy plus
Exubera, or Exubera alone.
 This suggests that some patients may achieve adequate glycemic control on
inhaled insulin alone, thereby simplifying their treatment regimen.
15OMEGA COLLEGE OF PHARMACY

16. SPECIAL POPULATIONS
SMOKING AND INHALED INSULIN
 It is estimated that 20% to 25% of individuals with diabetes are tobacco
smokers.
 Smoking induces both acute and chronic effects on the pulmonary system,
including vasoconstriction, changes in permeability, and remodeling of the
bronchioalveolar lining.
 Administration of inhaled insulin, nondiabetic chronic smokers have a higher
Cmax, greater absorption of insulin (AUC0-360), and shorter time to Cmax
nonsmokers.
 These data suggest that individuals who smoke would be at higher risk for
hypoglycemia when treated with inhaled insulin.
16OMEGA COLLEGE OF PHARMACY

17. RESPIRATORY DISEASE AND INHALED INSULIN
 Cough has been reported in 22% to 30% of patients with diabetes on
Exubera compared with 4% to 10% of patients with diabetes on comparator
treatment. (Data on file)
 The cough tended to occur within seconds to minutes after Exubera
inhalation, and was generally rated as mild. The cough was rarely
productive and rarely occurred at night.
 Cough prevalence was greatest in the first month of use, then decreased by
20% to 40% over the next 3 months, and remained constant thereafter.
 In clinical studies, only 1.2% of patients discontinued Exubera because of
cough. Patients who cough while on Exubera do not, on average, have any
change in pulmonary function tests (PFTs) that distinguishes them from
those who do not cough.
17OMEGA COLLEGE OF PHARMACY

18. AGE AND INHALED INSULIN :
 Both lung volumes and diffusion capacity change as a function of
age. These changes can modulate both delivery of inhaled insulin to
the distal airways, as well as absorption of the insulin across the
alveolar epithelium.
 Henry et al demonstrated that in individuals with T2DM, increasing
age (>65 years) impacted the ability of inhaled insulin to lower
glucose levels compared to a younger population (age 18 to 45 years)
while Cmax and AUC0–360 were not different between the two groups.
 These results indicate that, in older patients, an increased inhaled
insulin dose may be required to achieve comparable diabetes control.
18OMEGA COLLEGE OF PHARMACY

19. ADVERSE EFFECTS
 Body weight
 Hypoglycemia
 Pulmonary function
 Insulin antibodies
19OMEGA COLLEGE OF PHARMACY

20. CONCLUSION
 Inhaled insulin is a novel route of insulin administration which
has the potential to become a therapeutic option in the
treatment of both T1DM and T2DM. Overall, clinical trials
have demonstrated that inhaled insulin is noninferior to
subcutaneous insulin for improving glycemic control.
 Inhaled insulin also serves as relevant adjuvant therapy in
individuals with T2DM suboptimally controlled on oral
therapy. The most notable advantage of inhaled insulin over
subcutaneous insulin therapy is that it is well accepted by
patients and improves overall satisfaction scores. Thus,
availability of inhaled insulin may translate to improved
diabetes control and decrease the risk of long-term diabetes
complications.
20OMEGA COLLEGE OF PHARMACY

21. REFERENCES
1. Lucy D Mastrandrea, Inhaled insulin: overview of a novel
route of insulin administration, Mar 3, 2010, pg.no. 47–58.
2. Gowtham .T, Rafi Khan .P, Gopi Chand .K and
Nagasaraswathi .M, Facts of inhaled insulin, Journal of
Applied Pharmaceutical Science, 2011, 1(10), pg. no. 18-23.
3. Laura Zemany , MD and Martin J Abrahamson ,MD, Inhaled
Insulin—A New Insulin Delivery System, Research Fellow
and Medical Director Joslin Diabetes Center, Harvard
Medical School, pg. no. 48-51.
21OMEGA COLLEGE OF PHARMACY

22. THANKS for viewing the ppt
For more ppts
on pharma related topics plz contact
sarangi.dipu@gmail.com
Or find me at following link
www.facebook.com/sarangi.dipu
22OMEGA COLLEGE OF PHARMACY