Mechanistic Physiologically Based Pharmacokinetic Models in Development of Therapeutic Monoclonal Antibodies

摘要: Physiologically based pharmacokinetic (PBPK) models, with integrating the structural, in silico, and vitro physicochemical data of drugs physiological anatomical features body, provide a realistic characterization systemic disposition drugs. Therapeutic monoclonal antibodies (mAbs), as fastest growing class new therapeutic molecules, hold great promise for treatment variety diseases. This chapter first presents background history PBPK then details principles methods modelling mAbs. A number factors should be particularly considered developing models: distribution space, extravasation, lymphatic distribution, specific target binding. Then, discusses challenges modelling, by considering parameters, extravasation mechanisms, FcRn function. The also highlights two situations where minimal model enacts target-mediated drug (TMDD) either plasma or interstitial space. Keywords: distribution space; extravasation; FcRn function; lymphatic distribution; mechanistic models; minimal approach; specific binding; target-mediated disposition; therapeutic