Strategies to Overcome Efflux Pumps
Intestinal efflux pumps such as P-glycoprotein play a significant role in altering the absorption of a wide range of drugs. Anticancer agents, antibiotics, antivirals, calcium channel blockers, immunosuppressive agents, peptide drugs and several other therapeutic compounds have been reported to be substrates of one or more transmembrane efflux transporters.
Inhibition of these efflux pumps by various compounds can lead to enhanced absorption of several drugs across the intestine.
In this chapter, several efflux pump inhibitors such as low molecular mass inhibitors, polymeric inhibitors and advanced formulation approaches on how to overcome drug efflux are discussed.
KeywordsOral Bioavailability Efflux Pump Polymeric Inhibitor Efflux Pump Inhibitor Thiolated Chitosan
- Carreno-Gomez B. and Duncan R. Compositions with enhanced oral bioavailability. US patent, 2002.Google Scholar
- Föger F., Malaivijitnond S., Wannaprasert T., Huck C., Bernkop-Schnürch A., Werle M. (2008) Effect of oral paclitaxel in presence of a thiolated polymer on absorption and tumor growth in rats. J Drug Targeting, 16, (2), 149–55.Google Scholar
- Germann U.A., Shlyakhter D., Mason V.S., Zelle R.E., Duffy J.P., Galullo V., Armistead D.M., Saunders J.O., Boger J., Harding M.W. (1997) Cellular and biochemical characterization of VX-710 as a chemosensitizer: Reversal of P-glycoprotein-mediated multidrug resistance in vitro. Anticancer Drugs, 8:125–140.PubMedCrossRefGoogle Scholar
- Grabovac V., Bernkop-Schnürch A. (2006) Thiolated polymers as effective inhibitors of intestinal Mrp2 efflux pump transporters. Sci Pharm, 74.Google Scholar
- Johnson B.M., Charman W.N., Porter C.J.H. (2002) An in vitro examination of the impact of polyehtylene glycol 400, pluronic P85 and vitamin E D-a-tocopheryl polyethylene glycol 1000 succinate on p-glycoprotein efflux and enterocyte-based metabolism in excised rat intestine. AAPS PharmSci, 4: 1–13.CrossRefGoogle Scholar
- Palmberger T.F., Hombach J., Bernkop-Schnürch A. (2008) Thiolated chitosan: Development and in vitro evaluation of an oral delivery system for acyclovir. Int J Pharm, 348(1–2):79–85.Google Scholar
- Shono Y., Nishihara H., Matsuda Y., Furukawa S., Okada N., Fujita T., Yamamoto A. (2004) Modulation of intestinal P- glycoprotein function by cremophor EL and other surfactants by an in vitro diffusion chamber method using the isolated rat intestinal membranes. J Pharm Sci, 93:877–885.PubMedCrossRefGoogle Scholar
- Werle M. (2008a) Polymeric and low molecular mass efflux pump inhibitors for oral drug delivery. J Pharm Sci, 97, (1), 60–70.Google Scholar
- Werle M. (2008b) Natural and synthetic polymers as inhibitors of drug efflux pumps. Pharm Res, 25, (3), 500–11.Google Scholar