A Critical View on In Vitro Analysis of P-glycoprotein (P-gp) Transport Kinetics
Publikation: Bidrag til tidsskrift › Review › Forskning › fagfællebedømt
Transport proteins expressed in the different barriers of the human body can have great implications on absorption, distribution, and excretion of drug compounds. Inhibition or saturation of a transporter can potentially alter these absorbtion, distribution, metabolism and elimination properties and thereby also the pharmacokinetic profile and bioavailability of drug compounds. P-glycoprotein (P-gp, ABCB1) is an efflux transporter which is present in most of the barriers of the body, including the small intestine, the blood-brain barrier, the liver, and the kidney. In all these tissues, P-gp may mediate efflux of drug compounds and may also be a potential site for drug-drug interactions. Consequently, there is a need to be able to predict the saturation and inhibition of P-gp and other transporters in vivo. For this purpose, Michaelis-Menten steady-state analysis has been applied to estimate kinetic parameters, such as Km and Vmax, for carrier-mediated transport, whereas half-maximal inhibitor concentration (IC50) and the disassociation constant for an inhibitor/P-gp complex (Ki) have been determined to estimate P-gp inhibition. This review addresses in vitro methods commonly used to study P-gp transport kinetics and aims at providing a critical evaluation of the application of steady-state Michaelis-Menten analysis of kinetic parameters for substrate/P-gp interactions.
Originalsprog | Engelsk |
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Tidsskrift | Journal of Pharmaceutical Sciences |
Vol/bind | 106 |
Udgave nummer | 9 |
Sider (fra-til) | 2257-2264 |
Antal sider | 8 |
ISSN | 0022-3549 |
DOI | |
Status | Udgivet - sep. 2017 |
ID: 185406152