title: Insulin degludec: pharmacokinetic properties in subjects with hepatic impairment.
abstract: OBJECTIVE
  Insulin degludec is a basal insulin with a slow and distinct absorption mechanism resulting in an ultra-long, flat, and stable pharmacokinetic profile in patients with diabetes mellitus. The aim of this study was to examine the effect of hepatic impairment on the single-dose pharmacokinetics of insulin degludec.
  
  
  METHODS
  Twenty-four subjects, allocated to one of four groups (n=6 per group) based on level of hepatic impairment (normal hepatic function, Child-Pugh grade A, B, or C), were administered a single subcutaneous dose of 0.4 U/kg insulin degludec. Blood samples up to 120 h post-dose and fractionated urine samples were collected to measure pharmacokinetic parameters.
  
  
  RESULTS
  No difference was observed in pharmacokinetic parameters [area under the 120-h serum insulin degludec concentration-time curve (AUC120 h), maximum insulin degludec concentration (C max), and apparent clearance (CL/F)] for subjects with impaired versus normal hepatic function after a single dose of insulin degludec. The geometric mean [coefficient of variation (CV) %] AUC120 h values were 89,092 (16), 83,327 (15), 88,944 (23), and 79,846 (19) pmol·h/L for normal hepatic function and mild, moderate, and severe hepatic impairment, respectively. Simulated steady-state insulin degludec pharmacokinetic profiles showed an even distribution of exposure across a 24-h dosing interval regardless of hepatic function status.
  
  
  CONCLUSIONS
  The ultra-long pharmacokinetic properties of insulin degludec were preserved in subjects with hepatic impairment and there were no statistically significant differences in absorption or clearance compared with subjects with normal hepatic function.
authors.affiliation: Dérer's Hospital, University Hospital Bratislava, Limbová 5, 83305, Bratislava 37, Slovakia, kupcova@vnet.sk.
authors.forename: Viera
authors.initials: V
authors.lastname: Kupčová
authors.forename: Gerhard
authors.initials: G
authors.lastname: Arold
authors.forename: Carsten
authors.initials: C
authors.lastname: Roepstorff
authors.forename: Malene
authors.initials: M
authors.lastname: Højbjerre
authors.forename: Søren
authors.initials: S
authors.lastname: Klim
authors.forename: Hanne
authors.initials: H
authors.lastname: Haahr
mesh_terms: D000328:Adult; D019540:Area Under Curve; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics*; D007279:Injections, Subcutaneous; D049528:Insulin, Long-Acting / Q000493:pharmacokinetics*; D008107:Liver Diseases / Q000503:physiopathology*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; C571886:insulin degludec