title: Enhanced absorption of Nasulin™, an ultrarapid-acting intranasal insulin formulation, using single nostril administration in normal subjects.
abstract: BACKGROUND
  This pharmacokinetic (PK) study was designed to investigate the maximum intranasal insulin dose that could be achieved by repeated doses in a single nostril of a nasal spray of recombinant regular human insulin 1% in combination with cyclopentadecalactone (CPE-215) 2%, a compound that enhances absorption of molecules across mucous membranes (Nasulin™, CPEX Pharmaceuticals, Inc.).
  
  
  METHODS
  A nine-period crossover study of 8 healthy, nonsmoking subjects (ages 18-50, body mass index <33 kg/m², weight >70 kg) were studied. In a fasted state, subjects were randomly given 25, 50, and 75 U in a single nostril on the first day and randomly given 50, 75, and 100 U doses utilizing both nostrils on two subsequent days. After a 45-minute PK assessment, subjects were given a meal. To determine the mechanism of enhanced absorption in a single nostril, a second study utilizing 24 subjects under similar conditions received 25 U, placebo (P) that included CPE-215 plus 25 U, and 50 U in a single nostril.
  
  
  RESULTS
  Single nostril administration revealed enhanced absorption with maximum concentrations (C(max)) of 13, 65, and 96 µU/ml for the 25, 50, and 75 U doses, respectively. Dual nostril administration in two cohorts resulted in C(max) of 31/42, 65/52, and 88/79 µU/ml for the 50, 75, and 100 U, respectively. In the second cohort, C(max) was 23, 19, 56 µU/ml for the 25, P + 25, and 50 U doses, respectively.
  
  
  CONCLUSIONS
  Repeated dosing in a single nostril resulted in enhanced absorption; this was not due to the increased CPE-215 but to the increased insulin administered.
authors.affiliation: CPEX Pharmaceuticals, Inc., Exeter, NH 03833, USA. rstote@cpexpharm.com
authors.forename: Robert
authors.initials: R
authors.lastname: Stote
authors.forename: Michael
authors.initials: M
authors.lastname: Miller
authors.forename: Thomas
authors.initials: T
authors.lastname: Marbury
authors.forename: Leon
authors.initials: L
authors.lastname: Shi
authors.forename: Poul
authors.initials: P
authors.lastname: Strange
mesh_terms: D000042:Absorption; D000281:Administration, Intranasal; D000293:Adolescent; D000328:Adult; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005240:Feasibility Studies; D006262:Health; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D007328:Insulin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D008875:Middle Aged; D059085:Nasal Sprays; D009666:Nose; D010919:Placebos; D013997:Time Factors; D055815:Young Adult
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D059085:Nasal Sprays; D010919:Placebos