Monoclonal Antibody Pharmacokinetics and Pharmacodynamics

TLDR

Monoclonal antibodies, already numbering over 20 FDA‑approved drugs and expected to double in the next decade, are prized for their solubility, stability, long half‑life, selectivity, and low toxicity, yet they face challenges such as poor oral bioavailability, incomplete absorption after injection, nonlinear distribution and elimination, and immunogenicity that can alter their pharmacokinetics and efficacy. This review summarizes the key determinants of monoclonal antibody pharmacokinetics and pharmacodynamics. Clinical Pharmacology & Therapeutics 2008; 84(5):548–558.

Abstract

More than 20 monoclonal antibodies have been approved as therapeutic drugs by the US Food and Drug Administration, and it is quite likely that the number of approved antibodies will double in the next 7–10 years. Antibody drugs show several desirable characteristics, including good solubility and stability, long persistence in the body, high selectivity and specificity, and low risk for bioconversion to toxic metabolites. However, many antibody drugs demonstrate attributes that complicate drug development, including very poor oral bioavailability, incomplete absorption following intramuscular or subcutaneous administration, nonlinear distribution, and nonlinear elimination. In addition, antibody administration often leads to an endogenous antibody response, which may alter the pharmacokinetics and efficacy of the therapeutic antibody. Antibodies have been developed for a wide range of disease conditions, with effects produced through a complex array of mechanisms. This article attempts to provide a brief overview of the main determinants of antibody pharmacokinetics and pharmacodynamics. Clinical Pharmacology & Therapeutics (2008); 84, 5, 548–558 doi:10.1038/clpt.2008.170