title: PROMAXX inhaled insulin: safe and efficacious administration with a commercially available dry powder inhaler.
abstract: OBJECTIVE
  We investigated the pharmacokinetic (PK) and pharmacodynamic (PD) properties of recombinant human insulin inhalation powder (RHIIP), manufactured with PROMAXX technology, which allows formation of uniform protein microspheres.
  
  
  METHODS
  Thirty healthy male subjects [age 30 +/- 1 years (mean +/- s.e.), body mass index 24.2 +/- 0.3 kg/m(2)] in a randomized crossover study received 10 IU subcutaneous regular human insulin (SCIns) and 6.5 mg of RHIIP [187 IU, Cyclohaler dry powder inhaler (DPI)] under euglycaemic glucose clamp conditions. Subjects were trained to inhale RHIIP with a flow rate of 90 +/- 30 l/min prior to dosing.
  
  
  RESULTS
  Inhalation of RHIIP was well tolerated with no episode of cough or shortness of breath. RHIIP showed a faster onset of action than SCIns [time to reach 10% of total area under the glucose infusion rate (GIR) curves 73 +/- 2 vs. 95 +/- 3 min, time to maximal metabolic effect (T(max)GIR) 173 +/- 13 vs. 218 +/- 9 min, both p < 0.0001]. Duration of action (371 +/- 11 vs. 366 +/- 7 min) and total metabolic effect (AUCGIR0-10 h 2734 +/- 274 vs. 2482 +/- 155 mg/kg) were comparable. PK results were in accordance with the PD findings. Relative bioavailability (BA) of RHIIP was 12 +/- 2%, and relative biopotency (BP) was 6 +/- 1%.
  
  
  CONCLUSIONS
  PROMAXX technology allowed for safe and efficacious administration of RHIIP to the deep lung with an off-the-shelf DPI. RHIIP showed a fast onset of action and BA/BP comparable to that reported for other inhaled insulin formulations using specifically designed inhalers. Improvements in the insulin delivery technique might allow to optimize drug application in all cases with even higher BA/BP with RHIIP.
authors.affiliation: Profil Institute for Metabolic Research, Neuss, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Heise
authors.forename: A
authors.initials: A
authors.lastname: Brugger
authors.forename: C
authors.initials: C
authors.lastname: Cook
authors.forename: U
authors.initials: U
authors.lastname: Eckers
authors.forename: A
authors.initials: A
authors.lastname: Hutchcraft
authors.forename: L
authors.initials: L
authors.lastname: Nosek
authors.forename: K
authors.initials: K
authors.lastname: Rave
authors.forename: J
authors.initials: J
authors.lastname: Troeger
authors.forename: P
authors.initials: P
authors.lastname: Valaitis
authors.forename: S
authors.initials: S
authors.lastname: White
authors.forename: L
authors.initials: L
authors.lastname: Heinemann
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D002096:C-Peptide / Q000097:blood; D018592:Cross-Over Studies; D005858:Germany; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage*; D008297:Male; D008863:Microspheres; D009330:Nebulizers and Vaporizers; D016896:Treatment Outcome
chemical_list: D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin