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Therapeutic monoclonal antibodies (mAbs) have been successfully applied to treat various diseases and shown a promising prospect in medical treatment. MAbs have some unique characteristics when compared with small chemical drugs, and their pharmacokinetic (PK) properties are much more complex than those of small chemical drugs, whose eliminations are usually linear. In this study, a new model was established through taking into account the mechanisms of the elimination of mAbs. The proposed model was applied to the modeling and simulation of two kinds of mAbs, including bevacizumab and etanercept, in PK studies of healthy volunteers and eligible patients, and the classical linear compartment model was set as control. The goodness-of-fit of the fitting concentration-time curve of mAbs was calculated to verify the accuracy of both models during the modeling and simulation. The accuracy of the proposed model was better than that of classical linear compartment model in healthy volunteers and even much better in patients. The proposed model demonstrates a stronger ability in the modeling and simulation of mAbs, and may provide a new option for the PK studies of those reagents.