Significance of Protein Binding in Pharmacokinetics and Pharmacodynamics

The significance of plasma protein binding on drug efficacy and, subsequently, the clinical relevance of changes in protein binding has been controversially discussed for decades. The uncertainty concerning the impact of plasma protein binding on a drug's pharmacological activity is, in part, related to the approach used when investigating and interpreting protein binding effects in vitro and in vivo. Frequently, a generalized one‐size‐fits‐all approach, such as “protein binding does matter/does not matter,” may not be applicable. An appropriate analysis requires careful consideration of both pharmacokinetic and pharmacodynamic processes, as they both contribute to the safety and efficacy of drugs. Therefore, the aim of this article is to provide a concise review of the theoretical concepts of protein binding, and to discuss relevant examples where applicable. © 2009 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1107-1122, 2010