Absorption and Metabolic Effect of Inhaled Insulin
Intrapatient variability after inhalation via the Aerodose Insulin Inhaler in patients with type 2 diabetes
- Ayesh D. Perera, PHD1,
- Christoph Kapitza, MD2,
- Leszek Nosek, MD2,
- Robert S. Fishman, MD1,
- David A. Shapiro, MD1,
- Tim Heise, MD2 and
- Lutz Heinemann, PHD2
- 1Aerogen, Inc., Mountain View, California
- 2Profil Institute for Metabolic Research GmbH, Neuss, Germany
OBJECTIVE—To compare the intrapatient variability of the pharmacokinetic and pharmacodynamic responses to inhaled regular insulin (INH) delivered via the Aerodose Insulin Inhaler with that of subcutaneously injected regular insulin (SC) in patients with type 2 diabetes.
RESEARCH DESIGN AND METHODS—A total of 15 patients with type 2 diabetes (nonsmokers, 10 men, aged 47–77 years) received two 240-unit doses of INH, delivered via a clinical Aerodose Insulin Inhaler and two 24-unit doses of SC under euglycemic clamp conditions on four separate study days. Glucose infusion rates (GIRs) and serum insulin concentrations were monitored over the following 8 h. Comparisons of intrapatient coefficients of variation (CV) were used to assess the reproducibility of INH versus SC.
RESULTS—INH showed a bioavailability (0–8 h postdosing) of 16% and biopotency of 13% relative to SC. Comparison of the CVs (%) for area under the curve for serum insulin and GIR between INH and SC showed no significant differences between the treatments during 0–3 h (19% for INH versus 23% for SC) or 0–8 h (22% for INH versus 16% for SC). INH exhibited a shorter time to peak insulin concentration (Tmax [mean ± SD] 76 ± 51 vs. 193 ± 66 min) and shorter time to peak metabolic effect (TGIRmax 170 ± 53 vs. 244 ± 75 min) compared with SC (P < 0.001). No adverse events were observed.
CONCLUSIONS—Comparable dosing reproducibility and shorter time to peak action of INH compared with SC suggest that INH delivered via the Aerodose Insulin Inhaler can provide reliable preprandial dosing of insulin in patients with type 2 diabetes.
- AUC, area under the curve
- CV, coefficient of variation
- FEV1, forced expiratory volume in 1 s
- GIR, glucose infusion rate
- GIR-AUC, AUC for glucose infusion rate
- INH, inhaled regular insulin
- Ins-AUC, AUC for insulin
- PD, pharmacodynamic
- PK, pharmacokinetic
- RIA, radioimmunoassay
- SC, subcutaneously injected regular insulin
Address correspondence and reprint requests to Ayesh D. Perera, PhD, Aerogen, Inc., 2071 Stierlin Court, Mountain View, CA 94043. E-mail:.
Received for publication 6 June 2002 and accepted in revised form 22 August 2002.
A.D.P. and R.S.F. are employed by and own stock in Aerogen, the maker of the Aerodose Insulin Inhaler. C.K., L.N., T.H., and L.N. received financial support for conducting this study. D.A.S. is a paid consultant and stockholder of Aerogen.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
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