Time-action profile and patient assessment of inhaled insulin via the Exubera device in comparison with subcutaneously injected insulin aspart via the FlexPen device.
BACKGROUND
The goal of our investigation was to compare the pharmacokinetics/pharmacodynamics properties of and patient preference for insulin aspart applied with the FlexPen (Novo Nordisk, Bagsvaerd, Denmark) (IAFP) with pulmonary human insulin applied with the Exubera (Pfizer, New York, NY) device (HIEX).


METHODS
Twelve patients with diabetes (six with type 1 and six with type 2; eight men, four women; age, 54.5 +/- 11.0 years; duration of diabetes, 16.5 +/- 10.6 years; hemoglobin A1c, 7.5 +/- 0.7%; body mass index, 29.5 +/- 7.2 kg/m(2); mean +/- SD) participated in an open-label, randomized, euglycemic clamp study. The patients received 11 units of IAFP or a dose-equivalent of (3 + 1 mg) insulin from HIEX in a randomized sequence on two different study days. Insulin plasma levels and the required glucose infusion rate (GIR) were monitored for a time period of 6 h. In addition, the patients' individual ratings from 1 (excellent) to 5 (poor) regarding several different handling items were assessed using a questionnaire.


RESULTS
No significant difference in the pharmacokinetics/pharmacodynamics parameters could be observed between IAFP and HIEX within the first 120 min. In the second part of the clamp procedure, plasma insulin levels (area under the curve versus time [AUC]) and the GIR was significantly higher after HIEX compared with IAFP (insulin AUC(120-360), 66,232 +/- 4,521 vs. 48,852 +/- 2,999 pmol/L, P < 0.05; GIR AUC(120-360), 8,928 +/- 1,334 vs. 6,805 +/- 1,655 mg/kg/min). A superior patient judgment was obtained for the FlexPen with regard to trust in insulin delivery (2.3 +/- 1.1 vs. 2.8 +/- 1.0), trust in correct insulin dosing (1.8 +/- 1.1 vs. 2.6 +/- 0.9), size (2.3 +/- 1.1 vs. 3.6 +/- 0.9), and appearance of the device (2.4 +/- 1.0 vs. 3.8 +/- 0.9) (P < 0.05, respectively).


CONCLUSIONS
Insulin treatment with HIEX was found to have pharmacokinetics/pharmacodynamics properties comparable to IAFP. Both insulin administration technologies were overall evaluated positive, but most patients preferred IAFP.
Institute for Clinical Research and Development, Mainz, Germany. thomasf@ikfe.de
Thomas
T
Forst
Cloth
C
Hohberg
Thomas
T
Schöndorf
Marcus
M
Borchert
Senait
S
Forst
Werner
W
Roth
Barbara
B
Dehos
Andreas
A
Pfützner
D000280:Administration, Inhalation; D000281:Administration, Intranasal; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D018592:Cross-Over Studies; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D007279:Injections, Subcutaneous / Q000379:methods; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D061267:Insulin Aspart; D008297:Male; D008875:Middle Aged; D057240:Patient Preference; D010361:Patients
D001786:Blood Glucose; C473734:Exubera; D007004:Hypoglycemic Agents; D007328:Insulin; D061267:Insulin Aspart