Volume 1, Issue 20, 06/02/2009
What are the common efflux transporters involved in drug transport and drug-drug interactions?
The previous Drug Interactions Newsletter provided background information on common influx transporters used by some medications. This issue will focus on the common efflux cell membrane transporters that are used by many medications and are increasingly implicated in clinically relevant drug-drug interactions. As a review, many drug interactions that are not easily explained by an effect on the cytochrome P450 (CYP) enzyme system can now be explained by their influence on influx and efflux cell membrane transporters.(1-4) Often times these cell membrane transporters work in conjunction with drug metabolizing enzymes, such as the CYP enzyme system, for overall drug elimination.
Efflux cell membrane transporters are not only responsible for moving the parent drug and metabolites of some medications out of the cell, but may also contribute to drug resistance by diminishing the desired therapeutic or biologic effect.(2) As such, anything that prevents or inhibits a medication from being transported out of certain cells could result in excessive blood concentrations of the medication and cause undesired side effects. Moreover, an up-regulation of the number of efflux cell membrane transporters can result in the increased removal of medication, thereby resulting in an increased risk for therapeutic failure. In addition to inhibition or induction of CYP enzymes involved in drug metabolism, a number of medications can also inhibit or induce efflux cell membrane transporters. Therefore, clinicians need to become aware of the role and degree of influence that each of these systems have when investigating drug interactions....
There is a table available with this newsletter that summarizes all of the common efflux transporters, their genes, transcription factors, locations in the body and type of substrates they bind to.
Other keywords found in this issue: solute, carrier, organic, farnesoid, pregnane, apical membrane, basolateral membrane, cation, anion, intestine, liver, kidney, breast cancer, ATP, proximal tubule, steroid, receptor
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