Efavirenz reduces renal excretion of lamivudine in rats by inhibiting organic cation transporters (OCT, Oct) and multidrug and toxin extrusion proteins (MATE, Mate)
Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor used in first-line combination antiretroviral therapy (cART). It is usually administered with nucleoside reverse transcriptase inhibitors (NRTI), many of which are substrates of OCT uptake solute carriers (SLC22A) and MATE (SLC47A),...
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| description | Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor used in first-line combination antiretroviral therapy (cART). It is usually administered with nucleoside reverse transcriptase inhibitors (NRTI), many of which are substrates of OCT uptake solute carriers (SLC22A) and MATE (SLC47A), P-gp (MDR1, ABCB1), BCRP (ABCG2), or MRP2 (ABCC2) efflux transporters. The aim of this study was to evaluate the inhibitory potential of efavirenz towards these transporters and investigate its effects on the pharmacokinetics and tissue distribution of a known Oct/Mate substrate, lamivudine, in rats. Accumulation and transport assays showed that efavirenz inhibits the uptake of metformin by OCT1-, OCT2- and MATE1-expressing MDCK cells and reduces transcellular transport of lamivudine across OCT1/OCT2- and MATE1-expressing MDCK monolayers. Only negligible inhibition of MATE2-K was observed in HEK-MATE2-K cells. Efavirenz also reduced the efflux of calcein from MDCK-MRP2 cells, but had a rather weak inhibitory effect on Hoechst 33342 accumulation in MDCK-MDR1 and MDCK-BCRP cells. An in vivo pharmacokinetic interaction study in male Wistar rats revealed that intravenous injection of efavirenz or the control Oct/Mate inhibitor cimetidine significantly reduced the recovery of lamivudine in urine and greatly increased lamivudine retention in the renal tissue. Co-administration with efavirenz or cimetidine also increased the AUC0-∞ value and reduced total body clearance of lamivudine. These data suggest that efavirenz is a potent inhibitor of OCT/Oct and MATE/Mate transporters. Consequently, it can engage in drug-drug interactions that reduce renal excretion of co-administered substrates and enhance their retention in the kidneys, potentially compromising therapeutic safety. |
| doi_str_mv | 10.1371/journal.pone.0202706 |
| format | Article |
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It is usually administered with nucleoside reverse transcriptase inhibitors (NRTI), many of which are substrates of OCT uptake solute carriers (SLC22A) and MATE (SLC47A), P-gp (MDR1, ABCB1), BCRP (ABCG2), or MRP2 (ABCC2) efflux transporters. The aim of this study was to evaluate the inhibitory potential of efavirenz towards these transporters and investigate its effects on the pharmacokinetics and tissue distribution of a known Oct/Mate substrate, lamivudine, in rats. Accumulation and transport assays showed that efavirenz inhibits the uptake of metformin by OCT1-, OCT2- and MATE1-expressing MDCK cells and reduces transcellular transport of lamivudine across OCT1/OCT2- and MATE1-expressing MDCK monolayers. Only negligible inhibition of MATE2-K was observed in HEK-MATE2-K cells. Efavirenz also reduced the efflux of calcein from MDCK-MRP2 cells, but had a rather weak inhibitory effect on Hoechst 33342 accumulation in MDCK-MDR1 and MDCK-BCRP cells. An in vivo pharmacokinetic interaction study in male Wistar rats revealed that intravenous injection of efavirenz or the control Oct/Mate inhibitor cimetidine significantly reduced the recovery of lamivudine in urine and greatly increased lamivudine retention in the renal tissue. Co-administration with efavirenz or cimetidine also increased the AUC0-∞ value and reduced total body clearance of lamivudine. These data suggest that efavirenz is a potent inhibitor of OCT/Oct and MATE/Mate transporters. Consequently, it can engage in drug-drug interactions that reduce renal excretion of co-administered substrates and enhance their retention in the kidneys, potentially compromising therapeutic safety.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0202706</identifier><identifier>PMID: 30114293</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Accumulation ; Acquired immune deficiency syndrome ; AIDS ; Alkynes ; Animals ; Antiretroviral agents ; Antiretroviral drugs ; Antiretroviral therapy ; Area Under Curve ; Benzoxazines - pharmacology ; Biology and Life Sciences ; Calcein ; Cimetidine ; Cimetidine - pharmacology ; Consortia ; Cyclopropanes ; Dogs ; Drug therapy ; Efavirenz ; Efflux ; Excretion ; Extrusion ; Half-Life ; HEK293 Cells ; HIV ; Human immunodeficiency virus ; Humans ; In vivo methods and tests ; Inhibitors ; Intravenous administration ; Kidney - metabolism ; Kidneys ; Lamivudine ; Lamivudine - pharmacokinetics ; Lamivudine - pharmacology ; Lamivudine - urine ; Madin Darby Canine Kidney Cells ; Male ; MDR1 protein ; Medicine and Health Sciences ; Metformin ; Metformin - metabolism ; Metformin - pharmacology ; Multidrug Resistance-Associated Protein 2 ; Multidrug Resistance-Associated Proteins - antagonists & inhibitors ; Multidrug Resistance-Associated Proteins - metabolism ; Non-nucleoside reverse transcriptase inhibitors ; Nucleoside reverse transcriptase inhibitors ; Nucleosides ; Oct-2 protein ; Organic Cation Transport Proteins - antagonists & inhibitors ; Organic Cation Transport Proteins - metabolism ; P-Glycoprotein ; Pharmacokinetics ; Pharmacology ; Pharmacy ; Prescription drugs ; Proteins ; Rats ; Rats, Wistar ; Renal Elimination ; Renal function ; Research and Analysis Methods ; Retention ; Reverse Transcriptase Inhibitors - pharmacokinetics ; Reverse Transcriptase Inhibitors - pharmacology ; Reverse Transcriptase Inhibitors - urine ; RNA-directed DNA polymerase ; ROC Curve ; Substrates ; Toxicology ; Transport ; Urine</subject><ispartof>PloS one, 2018-08, Vol.13 (8), p.e0202706</ispartof><rights>2018 Ceckova et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2018 Ceckova et al 2018 Ceckova et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-8513242d5b379d14c5de9ec4201b8774a3b33cf7119365df59261226e48dc7273</citedby><cites>FETCH-LOGICAL-c526t-8513242d5b379d14c5de9ec4201b8774a3b33cf7119365df59261226e48dc7273</cites><orcidid>0000-0001-6712-097X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6095608/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6095608/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30114293$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Leggas, Markos</contributor><creatorcontrib>Ceckova, Martina</creatorcontrib><creatorcontrib>Reznicek, Josef</creatorcontrib><creatorcontrib>Deutsch, Birgit</creatorcontrib><creatorcontrib>Fromm, Martin F</creatorcontrib><creatorcontrib>Staud, Frantisek</creatorcontrib><title>Efavirenz reduces renal excretion of lamivudine in rats by inhibiting organic cation transporters (OCT, Oct) and multidrug and toxin extrusion proteins (MATE, Mate)</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor used in first-line combination antiretroviral therapy (cART). It is usually administered with nucleoside reverse transcriptase inhibitors (NRTI), many of which are substrates of OCT uptake solute carriers (SLC22A) and MATE (SLC47A), P-gp (MDR1, ABCB1), BCRP (ABCG2), or MRP2 (ABCC2) efflux transporters. The aim of this study was to evaluate the inhibitory potential of efavirenz towards these transporters and investigate its effects on the pharmacokinetics and tissue distribution of a known Oct/Mate substrate, lamivudine, in rats. Accumulation and transport assays showed that efavirenz inhibits the uptake of metformin by OCT1-, OCT2- and MATE1-expressing MDCK cells and reduces transcellular transport of lamivudine across OCT1/OCT2- and MATE1-expressing MDCK monolayers. Only negligible inhibition of MATE2-K was observed in HEK-MATE2-K cells. Efavirenz also reduced the efflux of calcein from MDCK-MRP2 cells, but had a rather weak inhibitory effect on Hoechst 33342 accumulation in MDCK-MDR1 and MDCK-BCRP cells. An in vivo pharmacokinetic interaction study in male Wistar rats revealed that intravenous injection of efavirenz or the control Oct/Mate inhibitor cimetidine significantly reduced the recovery of lamivudine in urine and greatly increased lamivudine retention in the renal tissue. Co-administration with efavirenz or cimetidine also increased the AUC0-∞ value and reduced total body clearance of lamivudine. These data suggest that efavirenz is a potent inhibitor of OCT/Oct and MATE/Mate transporters. Consequently, it can engage in drug-drug interactions that reduce renal excretion of co-administered substrates and enhance their retention in the kidneys, potentially compromising therapeutic safety.</description><subject>Accumulation</subject><subject>Acquired immune deficiency syndrome</subject><subject>AIDS</subject><subject>Alkynes</subject><subject>Animals</subject><subject>Antiretroviral agents</subject><subject>Antiretroviral drugs</subject><subject>Antiretroviral therapy</subject><subject>Area Under Curve</subject><subject>Benzoxazines - pharmacology</subject><subject>Biology and Life Sciences</subject><subject>Calcein</subject><subject>Cimetidine</subject><subject>Cimetidine - pharmacology</subject><subject>Consortia</subject><subject>Cyclopropanes</subject><subject>Dogs</subject><subject>Drug therapy</subject><subject>Efavirenz</subject><subject>Efflux</subject><subject>Excretion</subject><subject>Extrusion</subject><subject>Half-Life</subject><subject>HEK293 Cells</subject><subject>HIV</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>In vivo methods and tests</subject><subject>Inhibitors</subject><subject>Intravenous administration</subject><subject>Kidney - metabolism</subject><subject>Kidneys</subject><subject>Lamivudine</subject><subject>Lamivudine - pharmacokinetics</subject><subject>Lamivudine - pharmacology</subject><subject>Lamivudine - urine</subject><subject>Madin Darby Canine Kidney Cells</subject><subject>Male</subject><subject>MDR1 protein</subject><subject>Medicine and Health Sciences</subject><subject>Metformin</subject><subject>Metformin - metabolism</subject><subject>Metformin - pharmacology</subject><subject>Multidrug Resistance-Associated Protein 2</subject><subject>Multidrug Resistance-Associated Proteins - antagonists & inhibitors</subject><subject>Multidrug Resistance-Associated Proteins - metabolism</subject><subject>Non-nucleoside reverse transcriptase inhibitors</subject><subject>Nucleoside reverse transcriptase inhibitors</subject><subject>Nucleosides</subject><subject>Oct-2 protein</subject><subject>Organic Cation Transport Proteins - antagonists & inhibitors</subject><subject>Organic Cation Transport Proteins - metabolism</subject><subject>P-Glycoprotein</subject><subject>Pharmacokinetics</subject><subject>Pharmacology</subject><subject>Pharmacy</subject><subject>Prescription drugs</subject><subject>Proteins</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Renal Elimination</subject><subject>Renal function</subject><subject>Research and Analysis Methods</subject><subject>Retention</subject><subject>Reverse Transcriptase Inhibitors - pharmacokinetics</subject><subject>Reverse Transcriptase Inhibitors - pharmacology</subject><subject>Reverse Transcriptase Inhibitors - urine</subject><subject>RNA-directed DNA polymerase</subject><subject>ROC Curve</subject><subject>Substrates</subject><subject>Toxicology</subject><subject>Transport</subject><subject>Urine</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNp1ks1qGzEUhYfS0vy0b1BaQTcNxK5-ZjQzm0AwbhtI8MZdC410x5EZS1NJY5w-Tx80sj0JyaIrXUn3fPdyOFn2ieApYSX5vnaDt7Kb9s7CFFNMS8zfZKekZnTCKWZvX9Qn2VkIa4wLVnH-PjthmJCc1uw0-zdv5dZ4sH-RBz0oCOlMWAQ75SEaZ5FrUSc3ZjtoYwEZi7yMATUPqbw3jYnGrpDzK2mNQkoeJNFLG3rnI_iAvi1my0u0UPECSavRZuii0X5YHW7R7RIRdtEPYa_svYtgbFLdXS_nl-hORrj4kL1rZRfg43ieZ79_zJezX5Pbxc-b2fXtRBWUx0lVEEZzqouGlbUmuSo01KByiklTlWUuWcOYakuSfOGFbouackIph7zSqqQlO8--HLl954IYDQ6C4qqmJeWYpY6bY4d2ci16bzbSPwgnjTg8JBuE9NGoDoQuuQZOQLd5kee02DN02ySOwkTWKrGuxmlDswGtwCbbulfQ1z_W3IuV2wqO64LjKgG-jgDv_gwQ4n9Wzo9dyrsQPLTPEwgW-yQ9qcQ-SWJMUpJ9frnds-gpOuwRVwXIxg</recordid><startdate>20180816</startdate><enddate>20180816</enddate><creator>Ceckova, Martina</creator><creator>Reznicek, Josef</creator><creator>Deutsch, Birgit</creator><creator>Fromm, Martin F</creator><creator>Staud, Frantisek</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-6712-097X</orcidid></search><sort><creationdate>20180816</creationdate><title>Efavirenz reduces renal excretion of lamivudine in rats by inhibiting organic cation transporters (OCT, Oct) and multidrug and toxin extrusion proteins (MATE, Mate)</title><author>Ceckova, Martina ; Reznicek, Josef ; Deutsch, Birgit ; Fromm, Martin F ; Staud, Frantisek</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-8513242d5b379d14c5de9ec4201b8774a3b33cf7119365df59261226e48dc7273</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Accumulation</topic><topic>Acquired immune deficiency syndrome</topic><topic>AIDS</topic><topic>Alkynes</topic><topic>Animals</topic><topic>Antiretroviral agents</topic><topic>Antiretroviral drugs</topic><topic>Antiretroviral therapy</topic><topic>Area Under Curve</topic><topic>Benzoxazines - 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Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ceckova, Martina</au><au>Reznicek, Josef</au><au>Deutsch, Birgit</au><au>Fromm, Martin F</au><au>Staud, Frantisek</au><au>Leggas, Markos</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efavirenz reduces renal excretion of lamivudine in rats by inhibiting organic cation transporters (OCT, Oct) and multidrug and toxin extrusion proteins (MATE, Mate)</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2018-08-16</date><risdate>2018</risdate><volume>13</volume><issue>8</issue><spage>e0202706</spage><pages>e0202706-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor used in first-line combination antiretroviral therapy (cART). It is usually administered with nucleoside reverse transcriptase inhibitors (NRTI), many of which are substrates of OCT uptake solute carriers (SLC22A) and MATE (SLC47A), P-gp (MDR1, ABCB1), BCRP (ABCG2), or MRP2 (ABCC2) efflux transporters. The aim of this study was to evaluate the inhibitory potential of efavirenz towards these transporters and investigate its effects on the pharmacokinetics and tissue distribution of a known Oct/Mate substrate, lamivudine, in rats. Accumulation and transport assays showed that efavirenz inhibits the uptake of metformin by OCT1-, OCT2- and MATE1-expressing MDCK cells and reduces transcellular transport of lamivudine across OCT1/OCT2- and MATE1-expressing MDCK monolayers. Only negligible inhibition of MATE2-K was observed in HEK-MATE2-K cells. Efavirenz also reduced the efflux of calcein from MDCK-MRP2 cells, but had a rather weak inhibitory effect on Hoechst 33342 accumulation in MDCK-MDR1 and MDCK-BCRP cells. An in vivo pharmacokinetic interaction study in male Wistar rats revealed that intravenous injection of efavirenz or the control Oct/Mate inhibitor cimetidine significantly reduced the recovery of lamivudine in urine and greatly increased lamivudine retention in the renal tissue. Co-administration with efavirenz or cimetidine also increased the AUC0-∞ value and reduced total body clearance of lamivudine. These data suggest that efavirenz is a potent inhibitor of OCT/Oct and MATE/Mate transporters. Consequently, it can engage in drug-drug interactions that reduce renal excretion of co-administered substrates and enhance their retention in the kidneys, potentially compromising therapeutic safety.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>30114293</pmid><doi>10.1371/journal.pone.0202706</doi><orcidid>https://orcid.org/0000-0001-6712-097X</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2018-08, Vol.13 (8), p.e0202706 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2089272603 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS) Journals Open Access; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Accumulation Acquired immune deficiency syndrome AIDS Alkynes Animals Antiretroviral agents Antiretroviral drugs Antiretroviral therapy Area Under Curve Benzoxazines - pharmacology Biology and Life Sciences Calcein Cimetidine Cimetidine - pharmacology Consortia Cyclopropanes Dogs Drug therapy Efavirenz Efflux Excretion Extrusion Half-Life HEK293 Cells HIV Human immunodeficiency virus Humans In vivo methods and tests Inhibitors Intravenous administration Kidney - metabolism Kidneys Lamivudine Lamivudine - pharmacokinetics Lamivudine - pharmacology Lamivudine - urine Madin Darby Canine Kidney Cells Male MDR1 protein Medicine and Health Sciences Metformin Metformin - metabolism Metformin - pharmacology Multidrug Resistance-Associated Protein 2 Multidrug Resistance-Associated Proteins - antagonists & inhibitors Multidrug Resistance-Associated Proteins - metabolism Non-nucleoside reverse transcriptase inhibitors Nucleoside reverse transcriptase inhibitors Nucleosides Oct-2 protein Organic Cation Transport Proteins - antagonists & inhibitors Organic Cation Transport Proteins - metabolism P-Glycoprotein Pharmacokinetics Pharmacology Pharmacy Prescription drugs Proteins Rats Rats, Wistar Renal Elimination Renal function Research and Analysis Methods Retention Reverse Transcriptase Inhibitors - pharmacokinetics Reverse Transcriptase Inhibitors - pharmacology Reverse Transcriptase Inhibitors - urine RNA-directed DNA polymerase ROC Curve Substrates Toxicology Transport Urine |
| title | Efavirenz reduces renal excretion of lamivudine in rats by inhibiting organic cation transporters (OCT, Oct) and multidrug and toxin extrusion proteins (MATE, Mate) |
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