title: Open flow microperfusion: pharmacokinetics of human insulin and insulin detemir in the interstitial fluid of subcutaneous adipose tissue.
abstract: OBJECTIVE
  To compare the time profile of insulin detemir and human insulin concentrations in the interstitial fluid (ISF) of subcutaneous adipose tissue during constant i.v. infusion and to investigate the relationship between the pharmacokinetics of both insulin molecules in plasma and the ISF of subcutaneous adipose tissue.
  
  
  METHODS
  During a 6-h hyperinsulinaemic-euglycaemic clamp (plasma glucose level 8 mmol/l) human insulin (21 and 42 pmol/min/kg) or insulin detemir (209 and 417 pmol/min/kg) were infused i.v. in eight rats per dose level. Open flow microperfusion (OFM) was used to continuously assess interstitial insulin concentrations in subcutaneous adipose tissue.
  
  
  RESULTS
  At the lower infusion rate, insulin detemir appeared significantly later in the ISF than in the plasma (p < 0.05) and also appeared later in the ISF relative to human insulin (p < 0.005).
  
  
  CONCLUSIONS
  By using OFM we were able to monitor albumin-bound insulin detemir directly in the ISF of subcutaneous tissue and confirm its delayed transendothelial passage to a peripheral site of action.
authors.affiliation: Joanneum Research, Institute for Biomedicine and Health Sciences, Graz, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Höfferer
authors.forename: D
authors.initials: D
authors.lastname: Tutkur
authors.forename: C
authors.initials: C
authors.lastname: Fledelius
authors.forename: C L
authors.initials: CL
authors.lastname: Brand
authors.forename: T J
authors.initials: TJ
authors.lastname: Alsted
authors.forename: J
authors.initials: J
authors.lastname: Damgaard
authors.forename: E
authors.initials: E
authors.lastname: Nishimura
authors.forename: C B
authors.initials: CB
authors.lastname: Jeppesen
authors.forename: S I
authors.initials: SI
authors.lastname: Mautner
authors.forename: T R
authors.initials: TR
authors.lastname: Pieber
authors.forename: F
authors.initials: F
authors.lastname: Sinner
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism*; D015309:Glucose Clamp Technique; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D000069057:Insulin Detemir; D049528:Insulin, Long-Acting / Q000493:pharmacokinetics / Q000494:pharmacology*; D061386:Insulin, Regular, Human / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D010477:Perfusion / Q000295:instrumentation / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050151:Subcutaneous Fat / Q000187:drug effects* / Q000473:pathology; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; D061386:Insulin, Regular, Human; D000069057:Insulin Detemir
keywords: adipose tissue; animal pharmacology; dose-response relationships; insulin analogues; pharmacokinetics