Insulin Degludec: Pharmacokinetic Properties in Subjects with Hepatic Impairment

Abstract

Background and ObjectiveInsulin 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.MethodsTwenty-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.ResultsNo difference was observed in pharmacokinetic parameters [area under the 120-h serum insulin degludec concentration–time curve (AUC120 h), maximum insulin degludec concentration (Cmax), 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.ConclusionsThe 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.

A Review of the Pharmacological Properties of Insulin Degludec and Their Clinical Relevance

“…Serum, urine and dialysate (where relevant) concentrations of IDeg were measured using a specific sandwich enzyme-linked immunosorbent assay [21, 22, 27, 28]. …”

Clinical use of insulin degludec

“…Importantly, the ultra-long pharmacokinetic and pharmacodynamic properties of IDeg observed in patients with T1DM and T2DM are maintained in various subpopulations, such as the elderly and those with hepatic or renal impairment (including those with end-stage renal disease) [30][31][32]. The pharmacokinetic and pharmacodynamic properties of IDeg are maintained in both of its formulations, U100 and U200 [33].…”

“…IDeg is licensed for use in elderly patients (65 years of age) and is also suitable for use in patients with renal or hepatic impairment [34] as supported by clinical evidence, indicating that the pharmacokinetic characteristics of IDeg are preserved in these patient populations [30][31][32]. However, as recommended for other basal insulins [16,17], glucose-monitoring should be performed more frequently in these specific patient populations [34].…”

Diabetes Mellitus in Patients With Liver Cirrhosis: New Treatment Options

“…У исследуемых брали образцы крови и мочи в течение 120 ч после введения препарата для измерения параметров фармакокинетики ин-сулина. У пациентов с ПН не наблюдалось никаких различий в фармакокинетике (площади под кривой «концентрация-время» в течение 120 ч, макси-мальной концентрации инсулина, объема распре-деления и общего клиренса) по сравнению с паци-ентами с нормальной функцией печени [22]. Для сравнения метаболического контроля при использовании инсулина лизпро и рекомбинант-ного простого человеческого инсулина у пациентов с СД 2 типа и компенсированным неалкогольным ЦП S. Gentile и соавт.…”