title: Time-action profile of inhaled insulin in comparison with subcutaneously injected insulin lispro and regular human insulin.
abstract: 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.
authors.affiliation: Profil Institut für Stoffwechselforschung GmbH, Hellersbergstrasse 9, D-41460 Neuss, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Rave
authors.forename: Susanne
authors.initials: S
authors.lastname: Bott
authors.forename: Lutz
authors.initials: L
authors.lastname: Heinemann
authors.forename: Sue
authors.initials: S
authors.lastname: Sha
authors.forename: Reinhard H A
authors.initials: RH
authors.lastname: Becker
authors.forename: Susan A
authors.initials: SA
authors.lastname: Willavize
authors.forename: Tim
authors.initials: T
authors.lastname: Heise
mesh_terms: 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
chemical_list: D001786:Blood Glucose; C473734:Exubera; D007004:Hypoglycemic Agents; D007328:Insulin; D061268:Insulin Lispro; D005947:Glucose