Monoclonal Antibody Pharmacokinetics in Type 2 Diabetes Mellitus and Diabetic Nephropathy

Abstract

The incidence of diabetes mellitus (DM) is increasing worldwide, and both type 1 as well as type 2 DM patients are at high risk of developing diabetic nephropathy (DN). Although the effects of DM and DN have been well documented for low molecular weight proteins and albumin, there is limited information regarding the changes in the clearance of higher molecular weight proteins, including monoclonal antibodies (mAbs) and IgG, an antibody isotype. This review compiles the available literature describing the effects of DM and DN on the pharmacokinetics and pharmacodynamics of IgG and mAbs and the potential mechanisms underlying the effects of DM and DN on IgG/mAb renal and catabolic clearances. This review also highlights the role of the neonatal Fc receptor (FcRn) and endocytic receptors (megalin and cubilin) and the influence of cytokines on renal function and expression/function of these proteins.