PMID: 20645912Jul 22, 2010Paper

Using PET studies of P-gp function to elucidate mechanisms underlying the disposition of drugs

Current Topics in Medicinal Chemistry
Stina Syvänen, Margareta Hammarlund-Udenaes

Abstract

This paper discusses the basic principles of drug/P-glycoprotein (P-gp) interaction, focusing on the methodology and design of positron emission tomography (PET) studies investigating P-gp function. The requirements of a good PET P-gp radiotracer are also evaluated. (R)-[(11)C]verapamil is used as an example, as this drug is the most common tracer for P-gp studies, but [(11)C]loperamide, [(11)C]desmethyl-loperamide and other compounds are also mentioned. The article also discusses the various study designs that can be used for PET drug disposition studies, such as administration of the inhibitor before or after the radiolabeled drug (tracer) and the use of bolus injections or infusions. Concepts such as the unbound partition coefficient (K(p,uu)) and the volume of distribution of unbound drug in brain (V(u,brain)), which are not easily measured directly with PET, can be used to describe the impact of protein binding and non-specific binding on drug distribution in brain tissue. It is concluded that new imaging probes will be required if the role of PET in studies of the interactions of drugs with efflux transporters is to expand.

Citations

Jun 26, 2013·Pharmaceutical Research·Noora SjöstedtMarjo Yliperttula
Feb 21, 2013·ACS Chemical Neuroscience·Stina Syvänen, Jonas Eriksson
Jun 20, 2012·Annual Review of Analytical Chemistry·Courtney D Kuhnline SloanSusan M Lunte
Dec 18, 2014·International Journal for Parasitology. Drugs and Drug Resistance·Elizabeth E BygarskiBernadette F Ardelli
Apr 2, 2013·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Cristina BolzatiNicola Antonio Colabufo
Oct 16, 2012·Veterinary Parasitology·Bernadette F Ardelli, Roger K Prichard
Sep 7, 2013·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Ryota KikuchiJ Cory Kalvass
Feb 11, 2014·Current Protocols in Pharmacology·Alan M Palmer, Mohammad S Alavijeh
Sep 24, 2016·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Syahir MansorAdriaan A Lammertsma
May 17, 2011·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Tadayuki TakashimaYasuyoshi Watanabe
Dec 20, 2014·Analytical Chemistry·Anna NilssonPer E Andrén

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