Methotrexate Reduces the Clearance of Adalimumab by Increasing the Concentration of Neonatal Fc Receptor in Tissues

Purpose Although pharmacokinetic (PK) interaction effects of methotrexate (MTX) on adalimumab have been found, the mechanism of these effects is still unclear. In this work, effects of MTX on the concentration of neonatal Fc receptor (FcRn) and the role of FcRn in the interaction between MTX and adalimumab were investigated. Methods The experiment was performed in rats whose FcRn had normal physiological function and also in rats whose FcRn was blocked with FcRn antibody. Rats were randomly assigned to receive placebo or 0.2 mg/kg MTX orally every week while taking one abdominal subcutaneous injection of 0.5 mg/kg adalimumab. The FcRn concentration in tissues and the PK parameters of adalimumab were compared between MTX-treated and placebo groups. Results In rats with normally functioning FcRn, the concentrations of FcRn were significantly increased in the liver (F=105.5, p =0.000) and kidney (F=996.312, p =0.000) after treatment with MTX, and the clearance (CL/F) of adalimumab was decreased accordingly (F=4.423, p =0.048). However, in rats injected with FcRn antibody, the concentrations of FcRn in MTX-treated rats were close to that of the placebo rats in the tissues of the liver (F=1.279, p =0.268) and kidney (F=0.661, p =0.424). The CL/F of adalimumab in rats was also not affected by MTX (F=0.002, p =0.961). Conclusions FcRn may play a vital role in the interaction between adalimumab and MTX.