Determination of P-glycoprotein inhibition by excipients and their combinations using an integrated high-throughput process

Journal of Pharmaceutical Sciences
Szu-Wen WangHongming Chen

Abstract

Excipients often used in pharmaceutical formulations have been reported to have inhibitory effects on P-glycoprotein, an important membrane-associated transport protein. Because inhibition of efflux transporters can have an effect on drug bioavailability, identification of these excipients and their extent of inhibition are therefore important for pharmaceutical development. We have developed an automated and integrated high-throughput process for identifying these excipients and their combinations. Common excipients containing polyethylene glycol (PEG) in the chemical structure were screened using a cytotoxic cell growth assay, and excipients giving inhibition were further combined to identify synergistic effects. Our screens identified excipients previously reported to inhibit P-glycoprotein, such as PEG stearates, PEG fatty acid esters, polysorbates, and poloxamers. We also found new excipients, such as those in the PEG glyceryl fatty acid family, which were among the best inhibitors identified. Dose-response studies of these compounds and of cyclosporin A indicated that the extent of inhibition depended logarithmically on the concentration. This suggests a similar mechanism by which inhibition is obtained, despite widely va...Continue Reading

References

Aug 9, 1995·International Journal of Cancer. Journal International Du Cancer·L E BuckinghamJ S Coon
Mar 4, 1997·Proceedings of the National Academy of Sciences of the United States of America·A SparreboomO van Tellingen
Jan 1, 1997·Cancer Chemotherapy and Pharmacology·B I SikicG Chen
Aug 8, 1998·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·J Van AsperenJ H Beijnen
Mar 8, 2000·International Journal of Clinical Pharmacology and Therapeutics·M F Fromm
Apr 16, 2002·Neonatal Network : NN·B Noerr
Sep 5, 2002·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Bhagwant D RegeJames E Polli
Dec 18, 2002·Journal of Pharmaceutical Sciences·Erin D HuggerRonald T Borchardt
Aug 23, 2003·Journal of Controlled Release : Official Journal of the Controlled Release Society·S A BarkerD Q M Craig

❮ Previous
Next ❯

Citations

Sep 3, 2013·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Susana M MartinsDomingos C Ferreira
Jul 12, 2012·Journal of Medicinal Chemistry·Xue-Qing ChenMichael J Hageman
Feb 25, 2009·AAPS PharmSciTech·Enas A MahmoudMagdy I Mohamed
Jul 9, 2013·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Martin BauerOliver Langer
Mar 8, 2014·Proceedings of the National Academy of Sciences of the United States of America·David Putnam
Jul 16, 2014·Biochemical Engineering Journal·Dongmei RenSzu-Wen Wang
May 24, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Shasha RaoClive A Prestidge
Oct 4, 2006·Expert Opinion on Drug Metabolism & Toxicology·Anna Seelig, Grégori Gerebtzoff
Aug 31, 2007·Drug Development and Industrial Pharmacy·Subrata MallickPintu K De
Jan 3, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Lindsey CrawfordDavid Putnam
Apr 21, 2012·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Virginia ZabaletaJuan M Irache
Apr 27, 2010·International Journal of Pharmaceutics·Jonathan GooleGregory T Knipp
May 16, 2009·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Saijie ZhuYuanying Pei
Jan 18, 2006·Journal of Controlled Release : Official Journal of the Controlled Release Society·Eva-Maria CollnotClaus-Michael Lehr
Sep 23, 2014·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Alfredo García-Arieta
Mar 26, 2013·Advanced Functional Materials·Dongmei RenSzu-Wen Wang
Nov 6, 2008·Journal of Biomedical Materials Research. Part a·Haizheng Zhao, Lin Yue Lanry Yung
Oct 23, 2013·Journal of Biomaterials Applications·Abeer JabaiahSzu-Wen Wang
Nov 7, 2020·Naunyn-Schmiedeberg's Archives of Pharmacology·Sureshbabu Ram Kumar PandianSelvaraj Kunjiappan

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.