Journal Article

Clinical Pharmacokinetics of Dulaglutide in Patients with Type 2 Diabetes: Analyses of Data from Clinical Trials

Martin, Jennifer, Loghin, Corina, Geiser, Jeanne S., Heathman, Michael A., Chien, Jenny Y., Cui, Xuewei, de la Peña, Amparo

2016

Overview

Background and Objective Dulaglutide is a long-acting glucagon-like peptide-1 receptor agonist administered as once-weekly subcutaneous injections for the treatment of type 2 diabetes (T2D). The clinical pharmacokinetics of dulaglutide were characterized in patients with T2D and healthy subjects. Methods The pharmacokinetics of dulaglutide were assessed throughout clinical development, including conventional pharmacokinetic analysis in clinical pharmacology studies and population pharmacokinetic analyses of data from combined phase 2 and phase 3 studies in patients with T2D. The effects of potential covariates on dulaglutide population pharmacokinetics were evaluated using nonlinear mixed-effects models. Results Dulaglutide gradually reached the maximum concentration in 48 h and had a terminal elimination half-life of 5 days. Steady state was achieved between the second and fourth doses. The accumulation ratio was 1.56 for the 1.5 mg dose. Intra-individual variability estimates for the area under the plasma concentration–time curve and the maximum concentration were both <17 % [coefficient of variation (CV)]. There was no difference in pharmacokinetics between injection sites (arm, thigh or abdomen). Dulaglutide pharmacokinetics were well described by a two-compartment model with first-order absorption and elimination. The population clearance was estimated at 0.126 L/h [inter-individual variability (CV) 33.8 %]. Age, body weight, sex, race and ethnicity did not influence dulaglutide pharmacokinetics to any clinically relevant degree. Conclusion The pharmacokinetics of dulaglutide support once-weekly administration in patients with T2D. The pharmacokinetic findings suggest that dose adjustment is not necessary on the basis of body weight, sex, age, race or ethnicity or site of injection.

• Publisher: Springer International Publishing,Springer Nature B.V
• Subject: Adult / Aged / Aged, 80 and over / Diabetes Mellitus, Type 2 - metabolism / Drug Administration Routes / Female / Glucagon-Like Peptides - administration & dosage / Glucagon-Like Peptides - analogs & derivatives / Glucagon-Like Peptides - blood / Glucagon-Like Peptides - pharmacokinetics / Humans / Hypoglycemic Agents - administration & dosage / Hypoglycemic Agents - blood / Hypoglycemic Agents - pharmacokinetics / Immunoglobulin Fc Fragments - administration & dosage / Immunoglobulin Fc Fragments - blood / Internal Medicine / Male / Medicine / Medicine & Public Health / Middle Aged / Original Research Article / Pharmacology/Toxicology / Pharmacotherapy / Recombinant Fusion Proteins - administration & dosage / Recombinant Fusion Proteins - blood / Recombinant Fusion Proteins - pharmacokinetics / Young Adult