Biopharmaceutical Factors Involved in the Disposition of Mycophenolic Acid: A Comprehensive Review of ADME Properties and Their Potential Impact on Mycophenolic Acid Plasma Exposure

Mycophenolic acid (MPA) is an approved drug widely used as an immunosuppressant agent for the prevention of rejection in organ transplant patients and for managing various autoimmune disorders. Pharma-cological studies have shown that the plasma exposure of MPA is critical to to maintaining its efficacy, leading to a significant focus on MPA therapeutic drug monitoring (TDM) in clinical practice. Additionally, many papers have been published regarding MPA's absorption, distribution, metabolism, and elimination (ADME) characteristics, which are the key disposition factors affecting the plasma exposure of MPA. In this paper, we synthesize the current data and information in the literature on the ADME properties of MPA and discuss their implications for MPA's TDM. We also analyze the disposition of MPA major metabolites mycophenolic acid-glucuronide (MPAG), and acyl-glucuronide (AcMPAG), highlighting the key factors that affect MPA plasma exposure, including the influence of transporters, namely Multidrug Resistance-Associated Protein 2 (MRP2), Breast Cancer Resistance Protein (BCRP), Organic Anion-Transporting Polypeptides (OATPs), metabolic en-zymes (i.e., UDP-Glucuronosyltransferases (UGTs)), enterohepatic recycling (EHR), and protein binding. We expect to provide researchers with a comprehensive understanding of factors that could affect MPA's TDM to ensure its efficacy.