Tutorial on Monoclonal Antibody Pharmacokinetics and Its Considerations in Early Development

Abstract

The tutorial introduces the readers to the fundamentals of antibody pharmacokinetics (PK) in the context of drug development. Topics covered include an overview of antibody development, PK characteristics, and the application of antibody PK/pharmacodynamics (PD) in research and development decision-making. We also discuss the general considerations for planning a nonclinical PK program and describe the types of PK studies that should be performed during early development of monoclonal antibodies.

Figure 1

Schematic structure of IgG antibody: A simplified representation of IgG structure. V_L = variable light chain; V_H = variable heavy chain; C_H1 = constant heavy chain domain 1; C_H2 = constant heavy chain domain 2; C_H3 = constant heavy chain domain 3; CDR = complementary determining region (responsible for specific antigen binding); Fab = fragment antigen‐binding (Fab); F_c = fragment crystallizable region; F_v = fragment variable.

Figure 2

Representative PK profiles for linear and nonlinear clearance at the same doses. (a) The linear PK profiles with parallel elimination slopes. (b) The nonlinear PK profiles: the slope of the terminal phase decreases as the dose increases and approaches linear PK range as the dose reaches saturation dose level.

Figure 3

The alignment of major PK/PD‐related studies with the decision points of mAb development in both objectives and recommended studies.