Pharmaceutical Research

, Volume 32, Issue 8, pp 2477–2502 | Cite as

Transporter-Mediated Disposition of Opioids: Implications for Clinical Drug Interactions

  • Robert Gharavi
  • William Hedrich
  • Hongbing Wang
  • Hazem E. Hassan
Expert Review


Opioid-related deaths, abuse, and drug interactions are growing epidemic problems that have medical, social, and economic implications. Drug transporters play a major role in the disposition of many drugs, including opioids; hence they can modulate their pharmacokinetics, pharmacodynamics and their associated drug-drug interactions (DDIs). Our understanding of the interaction of transporters with many therapeutic agents is improving; however, investigating such interactions with opioids is progressing relatively slowly despite the alarming number of opioids-mediated DDIs that may be related to transporters. This review presents a comprehensive report of the current literature relating to opioids and their drug transporter interactions. Additionally, it highlights the emergence of transporters that are yet to be fully identified but may play prominent roles in the disposition of opioids, the growing interest in transporter genomics for opioids, and the potential implications of opioid-drug transporter interactions for cancer treatments. A better understanding of drug transporters interactions with opioids will provide greater insight into potential clinical DDIs and could help improve opioids safety and efficacy.


opioid abuse opioid DDI opioid drug transporters opioids and P-gp 





American Association for Poison Control Centers


Area under the curve


Blood–brain barrier


Breast cancer resistance protein


Permeability clearance into the brain


Central nervous system


Drug-drug interaction


Emergency department


Food and Drug Administration


Glucose transporters


Human embryonic kidney 293


Half maximal inhibitory concentration


Inhibition constant


Ratio of unbound drug in the brain to unbound drug in the blood








Methadone maintenance treatment


μ-opioid receptor


Multidrug resistance-associated proteins


National Survey on Drug Use and Health


Organic anion transporters


Organic anion-transporting polypeptides


Organic cation transporters








Volume of distribution within the brain


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Robert Gharavi
    • 1
    • 2
  • William Hedrich
    • 1
  • Hongbing Wang
    • 1
  • Hazem E. Hassan
    • 1
    • 3
  1. 1.Department of Pharmaceutical SciencesUniversity of Maryland School of PharmacyBaltimoreUSA
  2. 2.Clinical DevelopmentMedImmuneGaithersburgUSA
  3. 3.Department of Pharmaceutics and Industrial Pharmacy, Faculty of PharmacyHelwan UniversityCairoEgypt

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