Pharmaceutical Research

, 35:14 | Cite as

Indinavir Alters the Pharmacokinetics of Lamivudine Partially via Inhibition of Multidrug and Toxin Extrusion Protein 1 (MATE1)

  • Qing Li
  • Zhi Ye
  • Peng Zhu
  • Dong Guo
  • Hong Yang
  • Jin Huang
  • Wei Zhang
  • James E. Polli
  • Yan ShuEmail author
Research Paper



Lamivudine, a characterized substrate for human multidrug and toxin extrusion protein 1 (hMATE1) in vitro, was commonly used with indinavir as a therapy against human immunodeficiency virus (HIV). We aimed to investigate whether mouse MATE1 is involved in the disposition of lamivudine in vivo, and whether there is any transporter-mediated interaction between indinavir and lamivudine.


The role of MATE1 in the disposition of lamivudine was determined using Mate1 wild type (+/+) and knockout (−/−) mice. The inhibitory potencies of indinavir on lamivudine uptake mediated by OCT2 and MATE1 were determined in human embryonic kidney 293 (HEK 293) cells stably expressing these transporters. The role of MATE1 in the interaction between indinavir and lamivudine in vivo was determined using Mate1 (+/+) and Mate1 (−/−) mice.


The plasma concentrations and tissue accumulation of lamivudine were markedly elevated in Mate1 (−/−) mice as compared to those in Mate1 (+/+) mice. Indinavir significantly increased the pharmacokinetic exposure of lamivudine in mice; however, the effect by indinavir was significantly less pronounced in Mate1 (−/−) mice as compared to Mate1(+/+) mice.


MATE1 played an important role in lamivudine pharmacokinetics. Indinavir could cause drug-drug interaction with lamivudine in vivo via inhibition of MATE1 and additional mechanism.


drug-drug interaction indinavir lamivudine multidrug and toxin extrusion protein organic cation transporter 





Analysis of variance


4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide


The area under the plasma concentration-time curve


Body surface area


Maximum plasma concentration


Cytochrome P450


Drug-drug interactions


Dulbecco’s modified Eagle’s medium


Highly active antiretroviral therapy


Hepatitis B virus


Human equivalent dose

HEK-293 cells

Human embryonic kidney 293 cells


Human immunodeficiency virus


Human multidrug and toxin extrusion protein 1


Human organic cation transporter 2


Institutional Animal Care and Use Committee


Observed inhibitory constant


National Institutes of Health


Non-nucleoside reverse transcriptase inhibitors


Nucleoside reverse transcriptase inhibitors


Organic anion transporters


Phosphate buffered saline


Protease inhibitors


Standard deviation


Total body clearance




The time to maximal plasma concentration


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Clinical PharmacologyXiangya Hospital, Central South UniversityChangshaChina
  2. 2.Department of Pharmaceutical SciencesSchool of Pharmacy, University of Maryland at BaltimoreBaltimoreUSA
  3. 3.Department of AnesthesiologyXiangya Hospital, Central South UniversityChangshaChina

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