Model-based pharmacokinetic analysis of mosapride in beagle dogs following intravenous and oral administration
Mosapride is a widely used gastroprokinetic agent that acts as a selective 5-hydroxytryptamine type-4 receptor agonist. It is classified as a Biopharmaceutics Classification System class II drug, characterized by low solubility at physiological pH and high membrane permeability. Although the pharmacokinetics (PK) of mosapride have been investigated in humans and several animal species, pharmacokinetic studies in dogs remain limited. The aim of this study was to characterize the pharmacokinetic properties of mosapride following intravenous and oral administration in beagle dogs. Twenty beagle dogs were randomly assigned to intravenous (single dose of 1 mg) or oral (5 mg once daily) administration groups. Blood samples were collected at predetermined time points following dosing. Plasma concentrations of mosapride were quantified using liquid chromatography–tandem mass spectrometry. Conventional PK parameters were estimated using noncompartmental analysis with WinNonlin software. In addition, pharmacokinetic modeling was performed using the maximum likelihood expectation maximization algorithm implemented in ADAPT 5. The absorption rate constant of mosapride was estimated to be 3.14 ± 1.14 h⁻¹, and the oral bioavailability was approximately 1%. A one-compartment model adequately described the plasma concentration–time profiles following both intravenous and oral administration. The developed pharmacokinetic model successfully characterized mosapride disposition in dogs and may allow prediction of its pharmacokinetics under various conditions. Importantly, the model could also be used to predict the pharmacokinetics of modified-release formulations when combined with in vitro dissolution data. These findings suggest a potential strategy for mosapride formulation design. However, further studies are required to evaluate dose proportionality, interspecies pharmacokinetic differences between dogs and humans, and PK–PD relationships.
2026 Spring Convention