Influence of Genetic Polymorphisms on Mycophenolic Acid Pharmacokinetics and Patient Outcomes in Renal Transplantation

Title:Influence of Genetic Polymorphisms on Mycophenolic Acid Pharmacokinetics and Patient Outcomes in Renal Transplantation

Volume: 19 Issue: 14

Author(s): Miao Guo, Zi-Jie Wang, Hai-Wei Yang, Ling Meng, Ruo-Yun Tan, Min Gu*Ji-Fu Wei*

Affiliation:

• Department of Urology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029,China

• Research Division of Clinical Pharmacology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029,China

Keywords: Mycophenolic acid, genetic polymorphisms, pharmacokinetics, pharmacodynamics, renal transplantation, patient outcomes.

Abstract: Background: Mycophenolic Acid (MPA) is an immunosuppressive drug widely used in the treatment of organ transplantation and autoimmune diseases. Pharmacokinetics and pharmacodynamics of MPA varies between individuals, the potential reasons being the genetic polymorphisms in key enzymes, drug transporters and target proteins of MPA.

Objective: We try to provide pharmacogenomics information for drug selection and dose adjustment, aiming to improve drug efficacy and reduce side effects in clinical application of MPA.

Methods: In this review, we summarize the literatures in Pubmed that reported MPA-related Single Nucleotide Polymorphisms (SNPs) of renal transplant patients in recent 15 years.

Results: Genetic polymorphisms involving uridine diphosphate glucuronosyltransferase enzymes, organic anion transport polypeptides, multidrug resistance-associated protein 2, inosine monophosphate dehydrogenase and immune- response mediators may be associated with the metabolism, efficacy and toxicity of MPA, thus resulting in different MPA exposure and patient outcomes in renal transplantation.

Conclusion: Several SNPs show significant association with MPA pharmacokinetics and pharmacodynamics, but conflicting results are reported, and no studies on MPA genetic polymorphisms have been translated into clinical practice. More prospective studies are needed to clear the role of genetic polymorphisms on MPA in renal transplantation patients.

Cite this article as:

Guo Miao , Wang Zi-Jie , Yang Hai-Wei , Meng Ling , Tan Ruo-Yun , Gu Min *, Wei Ji-Fu *, Influence of Genetic Polymorphisms on Mycophenolic Acid Pharmacokinetics and Patient Outcomes in Renal Transplantation, Current Drug Metabolism 2018; 19 (14) . https://dx.doi.org/10.2174/1389200219666171227201608