Induction of Multiple Drug Transporters by Efavirenz
Efavirenz, an important component of human immunodeficiency virus 1 (HIV-1) therapy, causes substantial drug interactions as an inducer of cytochromes and the transporter ABCB1. So far its effect on the expression of other transporters is unknown. We therefore investigated the effect of long-term ex...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2009-01-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319312794 |
| _version_ | 1818030712944590848 |
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| author | Johanna Weiss Melanie Herzog Sonja König Caroline Henrike Storch Nahal Ketabi-Kiyanvash Walter Emil Haefeli |
| author_facet | Johanna Weiss Melanie Herzog Sonja König Caroline Henrike Storch Nahal Ketabi-Kiyanvash Walter Emil Haefeli |
| author_sort | Johanna Weiss |
| collection | DOAJ |
| description | Efavirenz, an important component of human immunodeficiency virus 1 (HIV-1) therapy, causes substantial drug interactions as an inducer of cytochromes and the transporter ABCB1. So far its effect on the expression of other transporters is unknown. We therefore investigated the effect of long-term exposure of cells to efavirenz on expression of a large number of important drug transporters and on cell proliferation as a surrogate of intracellular availability. LS180 cells were used as a surrogate for the major site of drug interactions and Jurkat cells were used as a surrogate for the main target cells of HIV therapy. Cells were treated with efavirenz over 4 weeks and mRNA expression of drug transporters was repeatedly quantified. After 4 weeks, efavirenz significantly up-regulated the mRNA of ABCB1, ABCG2, ABCC2, ABCC3, ABCC5, and SLCO3A1 in LS180 cells and ABCG2, ABCC1, ABCC4, ABCC5, and SLCO2B1 in Jurkat cells. However these changes in transporter expression did not influence cell proliferation indicating that intracellular efavirenz concentrations were likely not altered. Efavirenz induces mRNA expression of several drug transporters critically modulating the kinetics of other drugs. While these expressional changes will most likely not influence the efficiency of efavirenz itself, they might change the effect of other co-administered drugs. Keywords:: efavirenz, transporter, induction, drug–drug interaction |
| first_indexed | 2024-12-10T05:39:57Z |
| format | Article |
| id | doaj.art-59ff8b576555437f8d5cbe1ca14ea8e2 |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-10T05:39:57Z |
| publishDate | 2009-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-59ff8b576555437f8d5cbe1ca14ea8e22022-12-22T02:00:18ZengElsevierJournal of Pharmacological Sciences1347-86132009-01-011092242250Induction of Multiple Drug Transporters by EfavirenzJohanna Weiss0Melanie Herzog1Sonja König2Caroline Henrike Storch3Nahal Ketabi-Kiyanvash4Walter Emil Haefeli5Department of Internal Medicine VI, Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany; Corresponding author. johanna.weiss@med.uni-heidelberg.deDepartment of Internal Medicine VI, Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Im Neuenheimer Feld 410, D-69120 Heidelberg, GermanyDepartment of Internal Medicine VI, Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Im Neuenheimer Feld 410, D-69120 Heidelberg, GermanyDepartment of Internal Medicine VI, Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Im Neuenheimer Feld 410, D-69120 Heidelberg, GermanyDepartment of Internal Medicine VI, Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Im Neuenheimer Feld 410, D-69120 Heidelberg, GermanyDepartment of Internal Medicine VI, Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Im Neuenheimer Feld 410, D-69120 Heidelberg, GermanyEfavirenz, an important component of human immunodeficiency virus 1 (HIV-1) therapy, causes substantial drug interactions as an inducer of cytochromes and the transporter ABCB1. So far its effect on the expression of other transporters is unknown. We therefore investigated the effect of long-term exposure of cells to efavirenz on expression of a large number of important drug transporters and on cell proliferation as a surrogate of intracellular availability. LS180 cells were used as a surrogate for the major site of drug interactions and Jurkat cells were used as a surrogate for the main target cells of HIV therapy. Cells were treated with efavirenz over 4 weeks and mRNA expression of drug transporters was repeatedly quantified. After 4 weeks, efavirenz significantly up-regulated the mRNA of ABCB1, ABCG2, ABCC2, ABCC3, ABCC5, and SLCO3A1 in LS180 cells and ABCG2, ABCC1, ABCC4, ABCC5, and SLCO2B1 in Jurkat cells. However these changes in transporter expression did not influence cell proliferation indicating that intracellular efavirenz concentrations were likely not altered. Efavirenz induces mRNA expression of several drug transporters critically modulating the kinetics of other drugs. While these expressional changes will most likely not influence the efficiency of efavirenz itself, they might change the effect of other co-administered drugs. Keywords:: efavirenz, transporter, induction, drug–drug interactionhttp://www.sciencedirect.com/science/article/pii/S1347861319312794 |
| spellingShingle | Johanna Weiss Melanie Herzog Sonja König Caroline Henrike Storch Nahal Ketabi-Kiyanvash Walter Emil Haefeli Induction of Multiple Drug Transporters by Efavirenz Journal of Pharmacological Sciences |
| title | Induction of Multiple Drug Transporters by Efavirenz |
| title_full | Induction of Multiple Drug Transporters by Efavirenz |
| title_fullStr | Induction of Multiple Drug Transporters by Efavirenz |
| title_full_unstemmed | Induction of Multiple Drug Transporters by Efavirenz |
| title_short | Induction of Multiple Drug Transporters by Efavirenz |
| title_sort | induction of multiple drug transporters by efavirenz |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319312794 |
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