BACKGROUND: Imeglimin is a novel oral antidiabetic drug used to treat type 2 diabetes, targeting the mitochondrial bioenergetics. Imeglimin is mainly excreted unchanged by the kidneys and is a substrate of organic cation transporters, which are expressed in the kidney and the liver. OBJECTIVE: The aim of this study was to assess the effect of hepatic impairment on the pharmacokinetics of imeglimin. METHODS: An open-label, single-dose, parallel-group study was carried out in seven subjects with normal hepatic function and seven subjects with moderate hepatic impairment who received a single dose of imeglimin 1000 mg. Blood and urine samples were collected up to 48 h after imeglimin administration. Pharmacokinetics were determined using non-compartmental methods. RESULTS: Imeglimin maximum observed plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) in subjects with moderate hepatic impairment was 1.3-fold (90% confidence interval [CI] 1.05-1.60) and 1.5-fold (90% CI 1.19-1.82) higher than in subjects with normal hepatic function, but was not considered as clinically meaningful. Higher plasma exposure and amount of imeglimin renally excreted in moderate hepatic impaired subjects, associated with an unchanged elimination rate, suggests that this increase could be linked to a higher oral absorption and/or lower hepatic uptake in this population. CONCLUSIONS: Imeglimin was safe and well tolerated in all subjects. CLINICAL TRIAL REGISTRATION: EudraCT 2018-001950-83.
BACKGROUND: Imeglimin is a novel oral antidiabetic drug used to treat type 2 diabetes, targeting the mitochondrial bioenergetics. Imeglimin is mainly excreted unchanged by the kidneys and is a substrate of organic cation transporters, which are expressed in the kidney and the liver. OBJECTIVE: The aim of this study was to assess the effect of hepatic impairment on the pharmacokinetics of imeglimin. METHODS: An open-label, single-dose, parallel-group study was carried out in seven subjects with normal hepatic function and seven subjects with moderate hepatic impairment who received a single dose of imeglimin 1000 mg. Blood and urine samples were collected up to 48 h after imeglimin administration. Pharmacokinetics were determined using non-compartmental methods. RESULTS: Imeglimin maximum observed plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) in subjects with moderate hepatic impairment was 1.3-fold (90% confidence interval [CI] 1.05-1.60) and 1.5-fold (90% CI 1.19-1.82) higher than in subjects with normal hepatic function, but was not considered as clinically meaningful. Higher plasma exposure and amount of imeglimin renally excreted in moderate hepatic impaired subjects, associated with an unchanged elimination rate, suggests that this increase could be linked to a higher oral absorption and/or lower hepatic uptake in this population. CONCLUSIONS: Imeglimin was safe and well tolerated in all subjects. CLINICAL TRIAL REGISTRATION: EudraCT 2018-001950-83.
Authors: Sonia Pascual; José Such; Angel Esteban; Pedro Zapater; Juan A Casellas; José R Aparicio; Eva Girona; Ana Gutiérrez; Fernando Carnices; Jose M Palazón; Javier Sola-Vera; Miguel Pérez-Mateo Journal: Hepatogastroenterology Date: 2003 Sep-Oct