Interaction of Commonly Used Oral Molecular Excipients with P-glycoprotein
- 15 September 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in The AAPS Journal
- Vol. 23 (5), 1-12
- https://doi.org/10.1208/s12248-021-00631-8
Abstract
P-glycoprotein (P-gp) plays a critical role in drug oral bioavailability, and modulation of this transporter can alter the safety and/or efficacy profile of substrate drugs. Individual oral molecular excipients that inhibit P-gp function have been considered a mechanism for improving drug absorption, but a systematic evaluation of the interaction of excipients with P-gp is critical for informed selection of optimal formulations of proprietary and generic drug products. A library of 123 oral molecular excipients was screened for their ability to inhibit P-gp in two orthogonal cell-based assays. β-Cyclodextrin and light green SF yellowish were identified as modest inhibitors of P-gp with IC50 values of 168 μM (95% CI, 118-251 μM) and 204 μM (95% CI, 5.9-1745 μM), respectively. The lack of effect of most of the tested excipients on P-gp transport provides a wide selection of excipients for inclusion in oral formulations with minimal risk of influencing the oral bioavailability of P-gp substrates.Keywords
This publication has 60 references indexed in Scilit:
- Excipients with specialized functions for effective drug deliveryExpert Opinion on Drug Delivery, 2011
- Membrane transporters in drug developmentNature Reviews Drug Discovery, 2010
- Substrate-Dependent Effects of Human ABCB1 Coding PolymorphismsThe Journal of pharmacology and experimental therapeutics, 2008
- Impact of Cremophor-EL and Polysorbate-80 on Digoxin Permeability across Rat Jejunum: Delineation of Thermodynamic and Transporter Related Events Using the Reciprocal Permeability ApproachJournal of Pharmaceutical Sciences, 2007
- Overexpression of caveolin-1 increases plasma membrane fluidity and reduces P-glycoprotein function in Hs578T/DoxBiochemical and Biophysical Research Communications, 2004
- Involvement of cholesterol in the inhibitory effect of dimethyl‐β‐cyclodextrin on P‐glycoprotein and MRP2 function in Caco‐2 cellsFEBS Letters, 2003
- Role of P-Glycoprotein in PharmacokineticsClinical Pharmacokinetics, 2003
- Effects of Poly(ethylene glycol) on Efflux Transporter Activity in Caco‐2 Cell MonolayersJournal of Pharmaceutical Sciences, 2002
- Multidrug resistance in cancer: role of ATP–dependent transportersNature Reviews Cancer, 2002
- Drugs as P-glycoprotein substrates, inhibitors, and inducersDrug Metabolism Reviews, 2002