Time-action profile of inhaled insulin in comparison with subcutaneously injected insulin lispro and regular human insulin.
OBJECTIVE
This study compares the time-action profile of inhaled insulin (INH; Exubera) with that of subcutaneously injected insulin lispro (ILP) or regular human insulin (RHI) in healthy volunteers.


METHODS
In this open-label, randomized, three-way, crossover study, 17 healthy male volunteers were given each of the following treatments in random order: INH (6 mg), ILP (18 units), or RHI (18 units). Glucose infusion rates and serum insulin concentrations were monitored over 10 h.


RESULTS
INH had a faster onset of action than both RHI and ILP, as indicated by shorter time to early half-maximal effect (32 vs. 48 and 41 min, respectively; P < 0.001 for IHN vs. RHI and P < 0.05 for IHN vs. ILP). Time to maximal effect was comparable between INH and ILP (143 vs. 137 min; NS) but was shorter for INH than RHI (193 min; P < 0.01). The maximal metabolic effect of INH was comparable with RHI but lower than ILP (8.7 vs. 9.8 vs. 11.2 mg . kg(-1) . min(-1), respectively; P < 0.01 for INH vs. ILP). The duration of action of INH, indicated by time to late half-maximal effect (387 min), was longer than ILP (313 min; P < 0.01) and comparable to RHI (415 min; NS). Total glucodynamic effect after inhalation of INH was comparable to both ILP and RHI (NS). Relative bioefficacy of INH was 10% versus RHI and 11% versus ILP. No drug-related adverse events were observed.


CONCLUSIONS
INH had a faster onset of action than RHI or ILP and a duration of action longer than ILP and comparable to RHI. These characteristics suggest that inhaled insulin is suitable for prandial insulin supplementation in patients with diabetes.
Rave
Klaus
K
Profil Institut für Stoffwechselforschung GmbH, Hellersbergstrasse 9, D-41460 Neuss, Germany.
Bott
Susanne
S
Heinemann
Lutz
L
Sha
Sue
S
Becker
Reinhard H A
RH
Willavize
Susan A
SA
Heise
Tim
T
D000280:Administration, Inhalation; D000328:Adult; D001786:Blood Glucose / Q000187:drug effects; D018592:Cross-Over Studies; D005947:Glucose / Q000008:administration & dosage; D006801:Humans; D007003:Hypoglycemia / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D061268:Insulin Lispro; D008297:Male; D013997:Time Factors
D001786:Blood Glucose; C473734:Exubera; D007004:Hypoglycemic Agents; D007328:Insulin; D061268:Insulin Lispro; D005947:Glucose