Increased Exposure of Tacrolimus by Co-administered Mycophenolate Mofetil: Population Pharmacokinetic Analysis in Healthy Volunteers.

ABSTRACT: The objective of the study was to investigate the pharmacokinetic drug-drug interactions between tacrolimus (TAC) and mycophenolate mofetil (MMF) in healthy Korean male volunteers. Seventeen volunteers participated in a three-period, single-dose, and fixed sequence study. They sequentially received MMF, TAC, and the combination. Concentrations of TAC, mycophenolic acid (MPA), and its metabolites MPA 7-O-glucuronide and MPA acyl glucuronide were measured. The variants of CYP3A4, CYP3A5, SLCO1B1, SLCO1B3, ABCC2, UGT1A9, and UGT2B7 were genotyped. Drug interaction was evaluated with a non-compartmental analysis and population pharmacokinetic modelling to quantify the interaction effect. A total of 1,082 concentrations of those analytes were analysed. AUC0-inf of TAC increased by 22.1% (322.4?±?174.1 to 393.6?±?121.7?ng·h/mL; P?

SUBMITTER: Kim JH 

PROVIDER: S-EPMC5786104 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature