A minimal physiologically based pharmacokinetic model to study the combined effect of antibody size, charge, and binding affinity to FcRn/antigen on antibody pharmacokinetics.

ABSTRACT: Protein therapeutics have revolutionized the treatment of a wide range of diseases. While they have distinct physicochemical characteristics that influence their absorption, distribution, metabolism, and excretion (ADME) properties, the relationship between the physicochemical properties and PK is still largely unknown. In this work we present a minimal physiologically-based pharmacokinetic (mPBPK) model that incorporates a multivariate quantitative relation between a therapeutic's physicochemical parameters and its corresponding ADME properties. The model's compound-specific input includes molecular weight, molecular size (Stoke's radius), molecular charge, binding affinity to FcRn, and specific antigen affinity. Through derived and fitted empirical relationships, the model demonstrates t

SUBMITTER: Patidar K 

PROVIDER: S-EPMC11576895 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature