Understanding Voriconazole Metabolism: A Middle-Out Physiologically-Based Pharmacokinetic Modelling Framework Integrating In Vitro and Clinical Insights

CONCLUSION: This comprehensive parent-metabolite PBPK model of VRC quantitatively elucidated the complex metabolism of the drug and emphasised the substantial impact of the primary metabolites on VRC PK. The comprehensive approach combining bottom-up and middle-out modelling, thereby accounting for VRC autoinhibition, metabolite-mediated inhibition, and the impact of CYP2C19 genetic polymorphisms, enhances our understanding of VRC PK. Moreover, the model can be pivotal in designing further …