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This study quantifies the interaction between tacrolimus (TAC) and mycophenolate mofetil (MMF) in kidney transplant recipients. Concentrations of TAC, mycophenolic acid (MPA), and metabolites were analyzed and relevant genotypes were determined from 32 patients. A population model was developed to estimate the effect of interaction. Concentrations of TAC were simulated in clinical scenarios and dose-adjusted trough concentrations per dose (C/D) were compared. Effect of interaction was described as the inverse exponential relationship. Major determinants of trough levels of TAC were  CYP3A5  genotype and interaction with MPA. The absolute difference in C/D of TAC according to co-administered MMF was higher in  CYP3A5  non-expressers (0.55 ng/mL) than in  CYP3A5  expressers (0.35 ng/mL). The effect of MMF in determining the TAC exposure is more pronounced in  CYP3A5  non-expressers. Based on population pharmacokinetic model, we suggest the TAC dosing algorithm considering the effects of  CYP3A5  and MMF drug interaction in stable kidney transplant recipients.

scientific reports

Model based development of tacrolimus dosing algorithm considering CYP3A5 genotypes and mycophenolate mofetil drug interaction in stable kidney transplant recipients