Population Pharmacokinetic Modeling of Cotadutide: A Dual Agonist Peptide of Glucagon-Like Peptide and Glucagon Receptors Administered to Participants with Type II Diabetes Mellitus, Chronic Kidney Disease, Obesity and Non-Alcoholic Steatohepatitis

The mean apparent clearance of cotadutide is 1.05 L/h.

• A one-compartment model effectively describes cotadutide pharmacokinetics, confirmed through visual predictive checks.
• Mean values for cotadutide parameters include an apparent volume of distribution of 20.0 L, an absorption rate constant of 0.38 h, and a half-life of 13.3 hours.
• Body weight, alanine transaminase, albumin, anti-drug antibody titer values, formulation strength, injection device, and participant categories are significant factors affecting cotadutide pharmacokinetics.
• Higher body weight (e.g., 150 kg) is associated with approximately 30% lower exposure, while lower body weight (e.g., 66 kg) is associated with about 35% higher exposure compared to a reference weight of 96 kg.
• The impact of the identified covariates on pharmacokinetic parameters is considered statistically significant but not clinically meaningful.

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