title: Comparative pharmacokinetics and insulin action for three rapid-acting insulin analogs injected subcutaneously with and without hyaluronidase.
abstract: OBJECTIVE
  To compare the pharmacokinetics and glucodynamics of three rapid-acting insulin analogs (aspart, glulisine, and lispro) injected subcutaneously with or without recombinant human hyaluronidase (rHuPH20).
  
  
  METHODS
  This double-blind six-way crossover euglycemic glucose clamp study was conducted in 14 healthy volunteers. Each analog was injected subcutaneously (0.15 units/kg) with or without rHuPH20.
  
  
  RESULTS
  The commercial formulations had comparable insulin time-exposure and time-action profiles as follows: 50% exposure at 123-131 min and 50% total glucose infused at 183-186 min. With rHuPH20, the analogs had faster yet still comparable profiles: 50% exposure at 71-79 min and 50% glucose infused at 127-140 min. The accelerated absorption with rHuPH20 led to twice the exposure in the first hour and half the exposure beyond 2 h, which resulted in 13- to 25-min faster onset and 40- to 49-min shorter mean duration of insulin action.
  
  
  CONCLUSIONS
  Coinjection of rHuPH20 with rapid-acting analogs accelerated insulin exposure, producing an ultra-rapid time-action profile with a faster onset and shorter duration of insulin action.
authors.affiliation: Profil Institute for Clinical Research, Chula Vista, CA, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Morrow
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Muchmore
authors.forename: Marcus
authors.initials: M
authors.lastname: Hompesch
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Ludington
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Vaughn
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D061266:Insulin, Short-Acting / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D061266:Insulin, Short-Acting; D006821:Hyaluronoglucosaminidase