A Validated Whole-Body PBPK Model of Dextromethorphan and Its Metabolites for Genotype-Based Prediction of CYP2D6 Phenotype and Urinary Metabolic Ratio
Khaled Musa, Othman Noor Ashraf Noor, Mustafa Ibrahim, Anwar Saleh
2025Specialty journal of Pharmacognosy Phytochemistry and Biotechnology15 citationsDOIOpen Access PDF
Abstract
Cytochrome P450 2D6 (CYP2D6) is a major enzyme responsible for processing xenobiotics and contributes to the elimination of numerous therapeutic agents. Variation in the CYP2D6 gene produces substantial person-to-person differences in metabolic capacity and can influence how CYP2D6 probe compounds, such as dextromethorphan (DXM), are phenotyped. To explore these effects, we (i) assembled a large DXM pharmacokinetic dataset and (ii) created and verified a physiologically based pharmacokinetic (PB
Topics & Concepts
DextromethorphanCYP2D6PharmacokineticsDextrorphanPharmacologyPhysiologically based pharmacokinetic modellingChemistryCytochrome P450DrugMetaboliteEnzymeDrug metabolismXenobioticUrinary systemActive metabolitePhenotypeCYP2C9UrineMetabolic pathwayCoefficient of variationCYP3A4CYP2B6CytochromeDrug interactionPharmacogenetics and Drug MetabolismRespiratory and Cough-Related ResearchAsthma and respiratory diseases