Dose-Response Relationships of Inhaled Insulin Delivered via the Aerodose Insulin Inhaler and Subcutaneously Injected Insulin in Patients With Type 2 Diabetes

Kim, Dennis; Mudaliar, Sunder; Chinnapongse, Sithipol; Chu, Neelima V.; Boies, Sarah M.; Davis, Trent; Perera, A. G. U.; Fishman, Robert S.; Shapiro, D. A.; Henry, Robert R.

doi:10.2337/diacare.26.10.2842

Cited by 49 publications

(24 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A recent report showed dosedependent time to peak insulin levels with a right shift of the time-action profile for subcutaneously injected insulin (12). In contrast, we found that for oral insulin the time to maximum insulin concentrations, as well as time to peak metabolic effects, appear to be independent of the administered dose.…”

Section: Tolerability Of Insulin Inhalationcontrasting

confidence: 53%

Dose-Response Relationship of Oral Insulin Spray in Healthy Subjects

2005

View full text Add to dashboard Cite

ITAMAR RAZ, MD 1OBJECTIVE -To evaluate the pharmacodynamic and pharmacokinetic properties and the dose-ranging effects of an oral insulin spray in comparison with subcutaneous regular insulin.RESEARCH DESIGN AND METHODS -In this randomized, five-way, cross-over study, seven healthy volunteers were assessed under euglycemic clamp and received four different doses of oral spray and one dose of subcutaneous regular insulin.RESULTS -The time to maximum insulin concentration was shorter for oral insulin than for subcutaneous insulin (25.9 Ϯ 9 vs. 145.7 Ϯ 49.5 min, P Ͻ 0.05). Maximum serum insulin levels (C max ) were comparable between the subcutaneous and 20 puffs of oral insulin (39.1 Ϯ 19.6 vs. 34.0 Ϯ 7.4 U/ml, NS). The Ins-AUC 0 -120 (area under the curve from 0 to 120 min for serum insulin) (339.8 Ϯ 218, 681.3 Ϯ 407, and 1,586.7 Ϯ 8 U/ml, P Ͻ 0.05) and C max (7.6 Ϯ 2.8, 16.4 Ϯ 9.3, and 39.1 Ϯ 19.6 U/ml, P Ͻ 0.005) proved a dose-response relationship for the three doses of oral insulin (5, 10, and 20 puffs, respectively). Oral insulin had an earlier onset of action (31.7 Ϯ 12 vs. 77.8 Ϯ 3 min, P Ͻ 0.05), earlier peak (44.2 Ϯ 10 vs. 159.2 Ϯ 68 min, P Ͻ 0.05), and a shorter duration of action (85.1 Ϯ 25 vs. 319.2 Ϯ 45 min, P Ͻ 0.05) compared with subcutaneous insulin. The maximum metabolic effect (1.7 Ϯ 1.0, 3.09 Ϯ 1.7, and 4.6 Ϯ 1.5 mg ⅐ kg Ϫ1 ⅐ min Ϫ1 , P Ͻ 0.05) and the GIR-AUC 0 -120 (amount of glucose infused from 0 to 120 min) (106.7 Ϯ 74.3, 162.9 Ϯ 116.1, and 254 Ϯ 123 mg/kg) increased in a dose-dependent relationship for the three doses.CONCLUSIONS -Oral insulin was absorbed in direct relation to the amount given and had a faster onset and a shorter duration of action compared with subcutaneous regular insulin. A dose-response relationship in the absorption and metabolic effect of the oral insulin was noted. Diabetes Care 28:1353-1357, 2005I nsulin therapy is central to the treatment of people with type 1 (and some with type 2) diabetes. Intensive insulin regimen is proven to be associated with better long-term clinical outcomes; however, the inconvenience of multiple daily insulin injections might reduce compliance and possibly constitute an obstacle to obtaining good glycemic control.Therefore, alternative, noninjectable ways of insulin administration are being researched. One of these is oral insulin administration delivered by a spray device into the oropharyngeal cavity. It has the potential to more closely resemble the meal-stimulated physiologic insulin profile and therefore to become an attractive option and easy-to-use route for covering prandial insulin requirements. We used an oral insulin spray system that consists of an insulin formulation containing human recombinant insulin (Humulin R), a surfactant, a solubilizer, a micelle-creating agent, and emulsifying agents. All excipients are found on the FDA Generally Recognized as Safe list. The Generex RapidMist device, which is a proprietary pressurized Metered Dose Inhaler used to administer small-and largemolecule drugs to the buccal mucosa was u...

show abstract

Section: Tolerability Of Insulin Inhalationcontrasting

confidence: 53%

Dose-Response Relationship of Oral Insulin Spray in Healthy Subjects

2005

View full text Add to dashboard Cite

show abstract

“…Relative BA of insulin following inhalation of RHIIP was substantially different when determined using glucose infusion rates compared with the BA value determined using insulin concentrations. These phenomena were also observed in previous studies [7,8]. In these studies, BP of inhalation insulin showed a trend towards decreasing as doses for inhalation insulin increased for a given SC dose.…”

Section: Resultssupporting

confidence: 72%

“…The relationship between insulin concentration and glucose responses is sigmoidal and not linear (Hill's equation), and BP determined using glucose responses at high inhalation insulin doses are expected to be lower than those in lower dose ranges. For example in Kim's study [7], where the same insulin was used for both inhalation and SC dose routes, BPs obtained using glucose levels were approximately the same as BAs determined with insulin concentrations at the low inhalation dose (18.9% BP vs 19.1% BA at 80 IU inhalation dose). However, relative BP decreased as the inhalation insulin dose increased and was much lower than BA determined using insulin concentrations (14.3% BP vs 22.1% BA at 240 IU inhalation dose).…”

Section: Resultsmentioning

confidence: 99%

Differences in Relative Bioavailability (BA) of Inhalation Insulin Determined using Insulin and Glucose Levels Following Subcutaneous and Inhalation Administration in Humans

Cook¹,

Valaitis²,

Brugger³

2011

JBB

View full text Add to dashboard Cite

“…Several delivery systems are under development. The glucose-lowering effect following pulmonary delivery of insulin to patients with type 2 diabetes shows an appropriate dose-response relationship and appears to be more rapid than after subcutaneous injection of regular insulin, and similar to rapid-acting analogues [22,23]. Depending on the cost and convenience of devices, inhaled insulin could be an attractive way to provide bolus insulin in the future.…”

Section: The Futurementioning

confidence: 92%