Acid-reducing agents (ARA) such as antacids, histamine H2-receptor antagonists, and proton pump inhibitors are widely prescribed in several disease states. In the case of a basic drug with pH-dependent solubility, concomitant administration with an ARA may reduce drug absorption and systemic exposure, potentially resulting in loss of efficacy. Therefore, it is important to assess a drug’s susceptibility to pH-dependent DDIs during drug development, to characterize the DDI with clinical studies (as needed), and include appropriate instructions in the label. Given the ability of physiologically based biopharmaceutics modeling (PBBM) to directly link pharmacokinetics with physiological parameters, compound and formulation properties, these models are well positioned to address the DDI effects of ARA. In this presentation, we describe application of PBBM for biopharmaceutics risk assessment, and to guide formulation and clinical development strategies. We will present case studies and propose a pragmatic PBBM workflow to inform clinical development and regulatory decisions in ARA risk assessment.
Moderator:
Wei Zhu, Merck
Co-presenters:
Amitava Mitra, Janssen
Neil Parrott, Roche