The Role of Unbound Drug in Pharmacokinetics/Pharmacodynamics and in Therapy

Title: The Role of Unbound Drug in Pharmacokinetics/Pharmacodynamics and in Therapy

Volume: 12 Issue: 8

Author(s): Rosario Calvo, John C. Lukas, Monica Rodriguez, Nerea Leal and Elena Suarez

Affiliation:

Keywords: Unbound drug, protein binding, AGP variability, PK/PD

Abstract: The evolution of research on drug protein binding is discussed with the unbound concentration (Cu) and the unbound fraction (fu) as protagonists. Particular attention is paid to the mechanisms via which alterations in binding affect the pharmacokinetics (PK) and the effect, or independently the pharmacodynamics (PD). Apart from albumin, the important α-acid glycoprotein (AGP), as well as specific drug classes and applications in the clinic and development (routine monitoring, cancer and HIV therapy, allometry) are addressed. The flaws with the classical method of indirectly calculating the Cu or the unbound PK/PD parameters, based on the fu in vitro, are related to the intrinsic complexity and variability in the outcomes. Increased focus is urged on directly estimating the unbound PK/PD and also on using population statistical methods.

Cite this article as:

Calvo Rosario, Lukas C. John, Rodriguez Monica, Leal Nerea and Suarez Elena, The Role of Unbound Drug in Pharmacokinetics/Pharmacodynamics and in Therapy, Current Pharmaceutical Design 2006; 12 (8) . https://dx.doi.org/10.2174/138161206776055967