Mycophenolic acid(MPA)is mainly glucuronized by uridine diphosphate-glucuronosyltransferases(UGTs)into the phenolic MPA glucuronide(MPAG). MPAG is taken by SLC transporters such as organic anion-transporting polypeptide(OATP/gene SLCO), and is excreted by ABC transporters such as multidrug resistance protein 2(MRP2/gene ABCC2)and MRP3(gene ABCC3). MPAG pharmacokinetics are significantly influenced by SLCO1B1 and SLCO1B3 polymorphisms; however, MPA pharmacokinetics are not influenced by the polymorphisms of UGTs, SLCOs, and ABCCs. Even if transport or UGT activity caused by the mutation is reduced, another transport or metabolic pathway, which is an escape for MPA, may be present, and consequently MPA plasma concentration may not apparently have large changes by these polymorphisms. Dose predictions for renal transplant recipients are usually conducted to yield the total area under the plasma concentration-time curve(AUC0−12)values of MPA between 30 and 60mg・h/mL. Therefore, therapeutic drug monitoring(TDM)of MPA with this target AUC0−12 rather than gene analyses is an important in therapy considering the variability in MPA exposure.
