The role of unbound drug in pharmacokinetics/pharmacodynamics and in therapy

Current Pharmaceutical Design
Rosario CalvoElena Suarez

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 alpha-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.

Citations

Sep 24, 2013·Biochemical Pharmacology·Jianghong Fan, Inés A M de Lannoy
Apr 25, 2012·Journal of Pharmacokinetics and Pharmacodynamics·Oskar AlskärStephen B Duffull
Feb 5, 2013·The Surgeon : Journal of the Royal Colleges of Surgeons of Edinburgh and Ireland·Patrick H Conroy, James O'Rourke
Jun 27, 2013·Journal of Pharmaceutical Sciences·Tonika Bohnert, Liang-Shang Gan
Oct 24, 2009·Journal of Pharmaceutical Sciences·Stephan SchmidtHartmut Derendorf
Oct 22, 2014·Journal of Clinical Pharmacology·Stefanie HennigBruce Charles
Oct 27, 2007·British Journal of Clinical Pharmacology·Thomas Klitgaard, Tina G Nielsen

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