title: Steady state is reached within 2-3 days of once-daily administration of degludec, a basal insulin with an ultralong duration of action.
abstract: BACKGROUND
  Various factors influence the pharmacokinetic and pharmacodynamic properties of insulin analogs. The aim of the present study was to determine time to steady state of insulin degludec (IDeg), a basal insulin analog with an ultralong duration of action, after once-daily subcutaneous administration in subjects of varying age, diabetes type, and ethnicity.
  
  
  METHODS
  Time to steady state was analyzed in 195 subjects across five Phase I randomized single-center double-blind studies: three in subjects with type 1 diabetes (T1DM), including one in elderly subjects, and two in subjects with type 2 diabetes (T2DM), including one with African American and Hispanic/Latino subpopulations. Subjects received once-daily IDeg (100 U/mL, s.c.) at doses of 0.4-0.8 U/kg for 6-12 days. Time to clinical steady state was measured from first dose until the serum IDeg trough concentration exceeded 90% of the final plateau level. The IDeg concentrations were log-transformed and analyzed using a mixed-effects model with time from first dose and dose level (where applicable) as fixed effects, and subject as a random effect.
  
  
  RESULTS
  Steady state serum IDeg concentrations were reached after 2-3 days in all subjects. In trials with multiple dose levels, time to steady state was independent of dose level in T1DM (P = 0.51) and T2DM (P = 0.75).
  
  
  CONCLUSIONS
  Serum IDeg concentrations reached steady state within 2-3 days of once-daily subcutaneous administration in all subjects with T1DM or T2DM, including elderly and African American and Hispanic/Latino subjects. At steady state, serum IDeg concentrations were unchanged from day to day.
authors.affiliation: Profil, Neuss, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Heise
authors.affiliation: Medical University of Graz, Graz, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Korsatko
authors.affiliation: Profil, Neuss, Germany.
authors.forename: Leszek
authors.initials: L
authors.lastname: Nosek
authors.affiliation: Profil, Neuss, Germany.
authors.forename: Hans Veit
authors.initials: HV
authors.lastname: Coester
authors.affiliation: Medical University of Graz, Graz, Austria.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Deller
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Carsten
authors.initials: C
authors.lastname: Roepstorff
authors.affiliation: Aalborg, Denmark.
authors.forename: Stine
authors.initials: S
authors.lastname: Segel
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Rahul
authors.initials: R
authors.lastname: Kapur
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Hanne
authors.initials: H
authors.lastname: Haahr
authors.affiliation: Profil Institute for Clinical Research, Chula Vista, California, USA.
authors.forename: Marcus
authors.initials: M
authors.lastname: Hompesch
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American; D000368:Aged; D019540:Area Under Curve; D001786:Blood Glucose / Q000187:drug effects; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000208:ethnology / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000208:ethnology / Q000378:metabolism*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006630:Hispanic or Latino; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007279:Injections, Subcutaneous; D049528:Insulin, Long-Acting / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; C571886:insulin degludec
keywords: basal insulin; diabetes; pharmacokinetics; steady state; 基础胰岛素; 稳态; 糖尿病; 药物代谢动力学