Insulin through inhalation ppt

OMEGA COLLEGE OF PHARMACY 1

INSULIN THROUGH INHALATION.

A Concise Presentation

By

Mr. Deepak Sarangi M.Pharm.


CONTENTSIntroductionRole of insulinInhaled insulin devicesPharmacology of inhaled insulinPharmacokinetics of inhaled insulinGlucodynamics of inhaled insulinEquivalence dosing of inhaled insulinTreatment of diabetesSpecial populationAdverse effectsConclusionReferences


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.


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.


INHALED INSULIN DEVICESThe 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.



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.


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.


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.


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.


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.


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.


TREATMENT OF DIABETESThe 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.


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.


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.


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.


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.


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.


ADVERSE EFFECTS

Body weight

Hypoglycemia

Pulmonary function

Insulin antibodies


CONCLUSIONInhaled 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.


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.


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Insulin through inhalation ppt