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  • Title: Emerging significance of P-glycoprotein in understanding drug disposition and drug interactions in psychopharmacology.
    Author: Carson SW, Ousmanou AD, Hoyler SL.
    Journal: Psychopharmacol Bull; 2002; 36(1):67-81. PubMed ID: 12397848.
    Abstract:
    P-glycoprotein (P-gp) is a member of the superfamily of energy-dependent efflux protein pumps involved in the transport of a wide variety of endogenous and exogenous substrates. The role of P-gp has been extensively studied in the development of multidrug resistance (MDR) in cancer cells during chemotherapy. However, recent data suggest that P-gp is also present in normal tissue, such as the gut, blood-brain barrier, lymphocytes, liver, kidney, and other organs, where it plays a role in the absorption, distribution, metabolism, and elimination of a multitude of drugs. Psychotropic drugs, as well as many other drugs, act as substrates, inhibitors, or inducers of P-gp function. While there is a growing interest in developing inhibitors of this transporter as an approach to increasing drug bioavailability, the utility of exploiting inducers of the protein is less clear. Changes in P-gp transport activity have recently been linked to clinically significant drug-drug and drug-herb interactions. Because of its wide tissue distribution and its effect on drug disposition, clinicians should recognize the potential impact of P-gp modulation on the therapeutic efficacy and adverse events of psychopharmacologic agents that are substrates for this transporter. More research is needed in the field of psychopharmacology to classify central nervous system-active P-gp substrates and to characterize the utility of modulating P-gp activity at the blood-brain barrier.
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