Noni increased the systemic exposure of methotrexate in rats through inhibition on multi-drug resistance protein 2 (MRP 2) and breast cancer resistance protein (BCRP)

Abstract

Methotrexate (MTX) is an important immunosuppressant with narrow therapeutic window. The transport of MTX was associated with multi-drug resistance proteins (MRPs) and breast cancer resistance protein (BCRP). Noni fruit is a phenolics rich health food. This study set out to investigate the effect of noni juice on MTX pharmacokinetics and the underlying mechanisms. Rats were administered MTX with and without single dose or the 7th dose of noni juice (6mL/kg). The serum MTX concentrations were determined using a specific monoclonal fluorescence polarization immunoassay. The results revealed that single dose and multiple doses of noni juice significantly increased the AUC0–t, Cmax and MRT of MTX. A further inquiry into the underlying mechanism indicated that noni metabolites inhibited the activities of MRP 2 and BCRP. In conclusion, concomitant intake of noni juice significantly increased the systemic exposure of MTX through inhibition on MRP 2 and BCRP.