Monoclonal Antibody Pharmacokinetics and （单克隆抗体药物动力学和）.pdfVIP

state art nature publishing group Monoclonal Antibody Pharmacokinetics and Pharmacodynamics 1 2 3 W Wang , EQ Wang and JP Balthasar 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. IntroductIon antibodies may be further divided, again based on the structure Antibodies, which are also called immunoglobulins (Igs), are of their heavy chains, into four subclasses: IgG1, IgG2, IgG3, and large proteins used by the immune system to identify and neu- IgG4. Structural differences among IgG heavy chains lead to dif- tralize foreign objects such as bacteria and viruses. All Ig mol- ferences in subclass binding to Fc receptors and, consequently, ecule