Ultra-Long Pharmacokinetic Properties of Insulin Degludec are Comparable in Elderly Subjects and Younger Adults with Type 1 Diabetes Mellitus.
Background: Management of diabetes in elderly subjects is complex and careful management of glucose levels is of particular importance in this population because of an increased risk of diabetes-related complications and hypoglycaemia. Objective: The aim of this study was to evaluate the pharmacokin...
| Publicado en: | Drugs & Aging Vol. 31; no. 1; pp. 47 - 54 |
|---|---|
| Autores principales: | , , , , , , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Springer Nature
Jan2014
|
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=104130907&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 104130907 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 1170229X C5B jtl: Drugs & Aging issn: 1170229X maglogo: N pubinfo: dt: Jan2014 vid: 31 iid: 1 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 104130907 93435242 10.1007/s40266-013-0138-0 NLM24263619 PMC3880476 104130907 ppf: 47 ppct: 7 formats: fmt: @attributes: type: P tig: atl: Ultra-Long Pharmacokinetic Properties of Insulin Degludec are Comparable in Elderly Subjects and Younger Adults with Type 1 Diabetes Mellitus. aug: au: Korsatko, S. Deller, S. Mader, J. Glettler, K. Koehler, G. Treiber, G. Urschitz, M. Wolf, M. Hastrup, H. Søndergaard, F. Haahr, H. Pieber, T. affil: Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15 8036 Graz Austria sug: subj: Diabetes Mellitus, Type 1 Drug Therapy Insulin Classification Pharmacokinetics Insulin Administration and Dosage Human Aged Young Adult Aged: 65+ years ab: Background: Management of diabetes in elderly subjects is complex and careful management of glucose levels is of particular importance in this population because of an increased risk of diabetes-related complications and hypoglycaemia. Objective: The aim of this study was to evaluate the pharmacokinetic and pharmacodynamic properties of insulin degludec (IDeg), a basal insulin with an ultra-long duration of action, in elderly subjects with type 1 diabetes compared with younger adults. Methods: This trial was a randomised, double-blind, two-period, crossover trial conducted in a single centre and included both inpatient and outpatient periods. Subjects were men and women aged 18-35 years inclusive (younger adult group) or ≥65 years (elderly group) with type 1 diabetes who received IDeg (0.4 U/kg) via subcutaneous injection in the thigh once-daily for six days. Following 6-day dosing, a 26-hour euglycaemic glucose clamp procedure was conducted to evaluate the steady-state pharmacodynamic effects of IDeg. Blood samples were taken for pharmacokinetic analysis up to 120 h post-dose. Pharmacokinetic endpoints included the total exposure of IDeg, ie the area under the IDeg serum concentration curve during one dosing interval at steady state (AUC) ( τ = 0-24 h, equal to one dosing interval) and the maximum IDeg serum concentration at steady state (C). Pharmacodynamic endpoints included the total glucose-lowering effect of IDeg, ie the area under the glucose infusion rate (GIR) curve at steady state (AUC), and the maximum GIR at steady state (GIR). Results: Total exposure (AUC) and maximum concentration (C) of IDeg were comparable between elderly subjects and younger adults. Estimated mean age group ratios (elderly/younger adult) for AUC and C and corresponding two-sided 95 % confidence intervals (CIs) were 1.04 (95 % CI 0.73-1.47) and 1.02 (95 % CI 0.74-1.39), respectively. Mean AUC/AUC was 53 % in both younger adult and elderly subjects, showing that in both age groups IDeg exposure was evenly distributed across the first and second 12 h of the 24-hour dosing interval. No statistically significant differences were observed between younger adult and elderly subjects with regard to AUC (the primary endpoint of this study) and GIR. Estimated mean age group ratios (elderly/younger adult) for AUC and GIR and corresponding two-sided 95 % CIs were 0.78 (95 % CI 0.47-1.31) and 0.80 (95 % CI 0.54-1.17), respectively. Duration of action was beyond the clamp duration of 26 h in all subjects. Conclusions: The exposure of IDeg at steady state during once-daily dosing was similar in younger adult and elderly subjects. The glucose-lowering effect of IDeg was numerically lower in elderly subjects compared with younger adults, but no significant differences were observed between age groups. The ultra-long pharmacokinetic and pharmacodynamic properties of IDeg observed in younger adults were preserved in elderly subjects with type 1 diabetes. Clinical trials.gov number: NCT00964418 pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|