Details

Autor(en) / Beteiligte

• Heise, Tim
• Korsatko, Stefan
• Nosek, Leszek
• Coester, Hans Veit
• Deller, Sigrid
• Roepstorff, Carsten
• Segel, Stine
• Kapur, Rahul
• Haahr, Hanne
• Hompesch, Marcus

Titel

Steady state is reached within 2-3 days of once-daily administration of degludec, a basal insulin with an ultralong duration of action

Ist Teil von

• Journal of diabetes, 2016-01, Vol.8 (1), p.132-138

Ort / Verlag

Australia: Blackwell Publishing Ltd

Erscheinungsjahr

2016

Link zum Volltext

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• 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. 摘要 背景 各种因素都可以影响胰岛素类似物的药物代谢动力学与药效学特征。当前这项研究的目的是在不同年龄、糖尿病类型以及种族的受试者中每日1次皮下注射德谷胰岛素(insulin degludec,IDeg)(一种持续作用时间超长的基础胰岛素类似物)后测定他们达到稳态的时间。 方法 在195名横跨5项I期随机单中心双盲研究的受试者中分析达到稳态的时间:有3项研究是在1型糖尿病受试者中进行的,包括1项对老年受试者的研究,有2项研究是在2型糖尿病受试者中进行的,包括1项对非裔美国人与西班牙裔/拉丁美洲亚组人群的研究。受试者接受每日一次0.4‐0.8 U/kg剂量的IDeg(100 U/mL,皮下注射)共治疗6‐12日。测定了达到临床稳态的时间,即从第一次给药直到血清IDeg谷浓度超过90%最终峰值水平的时间。使用混合效应模型,将第一次给药后的时间以及剂量水平(能够使用的)作为固定效应,将受试者作为随机效应,记录与分析了IDeg的浓度变化。 结果 在所有的受试者中,经过2‐3日后血清IDeg浓度都达到了稳态。在多种剂量水平的试验中达到稳态的时间都不依赖于剂量水平,无论是在1型糖尿病(P = 0.51)还是2型糖尿病(P = 0.75)患者中。 结论 在所有的1型糖尿病或2型糖尿病受试者包括老年人、非裔美国人以及西班牙裔/拉丁美洲受试者中,每日1次皮下注射给药,2‐3日之后血清IDeg的浓度就可以达到稳态。在稳态下,血清IDeg的浓度日复一日都不会发生变化。