Modulation of human BCRP (ABCG2) activity by anti-HIV drugs

Publication type:
Journal article
Metadata:
Autoren
  • Johanna Weiss
  • Johanna Rose
  • Caroline Henrike Storch
  • Nahal Ketabi-Kiyanvash
  • Alexandra Sauer
  • Walter Emil Haefeli
  • Thomas Efferth
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000245011800011&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1093/jac/dkl474
eISSN
1460-2091
Externe Identifier
  • Clarivate Analytics Document Solution ID: 147OH
  • PubMed Identifier: 17202245
ISSN
0305-7453
Ausgabe der Veröffentlichung
2
Zeitschrift
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
Schlüsselwörter
  • HIV-protease inhibitors
  • non-nucleoside reverse transcriptase inhibitors
  • nucleoside reverse transcriptase inhibitors
  • nucleotide reverse transcriptase inhibitors
  • drug interactions
Paginierung
238 - 245
Datum der Veröffentlichung
2007
Status
Published
Titel
Modulation of human BCRP (ABCG2) activity by anti-HIV drugs
Sub types
  • Article
Ausgabe der Zeitschrift
59

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
  • J Weiss
  • J Rose
  • CH Storch
  • N Ketabi-Kiyanvash
  • A Sauer
  • WE Haefeli
  • T Efferth
DOI
10.1093/jac/dkl474
eISSN
1460-2091
ISSN
0305-7453
Ausgabe der Veröffentlichung
2
Zeitschrift
Journal of Antimicrobial Chemotherapy
Sprache
en
Online publication date
2006
Paginierung
238 - 245
Status
Published online
Herausgeber
Oxford University Press (OUP)
Herausgeber URL
http://dx.doi.org/10.1093/jac/dkl474
Datum der Datenerfassung
2017
Titel
Modulation of human BCRP (ABCG2) activity by anti-HIV drugs
Ausgabe der Zeitschrift
59

Data source: Crossref

Abstract
<h4>Objectives</h4>The safety and effectiveness of highly active antiretroviral therapy (HAART) is challenged by viral resistance to antiretrovirals and the frequent occurrence of drug interactions which may limit the access of these drugs to the target sites. In particular, drug distribution and elimination may be modified by active efflux transporters. While P-glycoprotein is well evaluated in this regard, the interaction of antiretrovirals with the ABC transporter BCRP (ABCG2) is far from being elucidated. The aim of this study was therefore to investigate the influence of all important anti-HIV drugs on BCRP activity in vitro in one assay to allow unrestricted comparison of the results.<h4>Methods</h4>BCRP inhibition was assessed by an increase in pheophorbide A accumulation in MDCKII-BCRP cells and compared with the corresponding parental cell line MDCKII lacking human BCRP.<h4>Results</h4>According to the IC(50) estimation, the rank order for BCRP inhibition was lopinavir > nelfinavir > delavirdine > efavirenz > saquinavir > atazanavir > amprenavir > abacavir. Whereas nevirapine and zidovudine exerted weak inhibition, the inhibitory potency for ritonavir and tipranavir could not be estimated due to their low solubility and all other tested compounds (indinavir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir and zalcitabine) were devoid of an effect.<h4>Conclusions</h4>Taken together, our study demonstrates significant inhibition of BCRP by many anti-HIV drugs. These results suggest that inhibition of BCRP might contribute to drug-drug interactions observed during HAART in vivo and possibly also the superior effectiveness of combination antiretroviral therapy.
Addresses
  • Department of Internal Medicine VI, Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany. johanna.weiss@med.uni-heidelberg.de
Autoren
  • Johanna Weiss
  • Johanna Rose
  • Caroline Henrike Storch
  • Nahal Ketabi-Kiyanvash
  • Alexandra Sauer
  • Walter Emil Haefeli
  • Thomas Efferth
  • Thomas Efferth
DOI
10.1093/jac/dkl474
eISSN
1460-2091
Externe Identifier
  • PubMed Identifier: 17202245
Open access
false
ISSN
0305-7453
Ausgabe der Veröffentlichung
2
Zeitschrift
The Journal of antimicrobial chemotherapy
Schlüsselwörter
  • Cell Line
  • Epithelial Cells
  • Animals
  • Dogs
  • Humans
  • Chlorophyll
  • ATP-Binding Cassette Transporters
  • Neoplasm Proteins
  • Anti-HIV Agents
  • Blotting, Western
  • Flow Cytometry
  • Transfection
  • Cell Survival
  • Drug Interactions
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
Sprache
eng
Medium
Print-Electronic
Online publication date
2007
Paginierung
238 - 245
Datum der Veröffentlichung
2007
Status
Published
Datum der Datenerfassung
2007
Titel
Modulation of human BCRP (ABCG2) activity by anti-HIV drugs.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
59

Data source: Europe PubMed Central

Abstract
OBJECTIVES: The safety and effectiveness of highly active antiretroviral therapy (HAART) is challenged by viral resistance to antiretrovirals and the frequent occurrence of drug interactions which may limit the access of these drugs to the target sites. In particular, drug distribution and elimination may be modified by active efflux transporters. While P-glycoprotein is well evaluated in this regard, the interaction of antiretrovirals with the ABC transporter BCRP (ABCG2) is far from being elucidated. The aim of this study was therefore to investigate the influence of all important anti-HIV drugs on BCRP activity in vitro in one assay to allow unrestricted comparison of the results. METHODS: BCRP inhibition was assessed by an increase in pheophorbide A accumulation in MDCKII-BCRP cells and compared with the corresponding parental cell line MDCKII lacking human BCRP. RESULTS: According to the IC(50) estimation, the rank order for BCRP inhibition was lopinavir > nelfinavir > delavirdine > efavirenz > saquinavir > atazanavir > amprenavir > abacavir. Whereas nevirapine and zidovudine exerted weak inhibition, the inhibitory potency for ritonavir and tipranavir could not be estimated due to their low solubility and all other tested compounds (indinavir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir and zalcitabine) were devoid of an effect. CONCLUSIONS: Taken together, our study demonstrates significant inhibition of BCRP by many anti-HIV drugs. These results suggest that inhibition of BCRP might contribute to drug-drug interactions observed during HAART in vivo and possibly also the superior effectiveness of combination antiretroviral therapy.
Autoren
  • Johanna Weiss
  • Johanna Rose
  • Caroline Henrike Storch
  • Nahal Ketabi-Kiyanvash
  • Alexandra Sauer
  • Walter Emil Haefeli
  • Thomas Efferth
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/17202245
DOI
10.1093/jac/dkl474
ISSN
0305-7453
Ausgabe der Veröffentlichung
2
Zeitschrift
J Antimicrob Chemother
Schlüsselwörter
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Animals
  • Anti-HIV Agents
  • Blotting, Western
  • Cell Line
  • Cell Survival
  • Chlorophyll
  • Dogs
  • Drug Interactions
  • Epithelial Cells
  • Flow Cytometry
  • Humans
  • Neoplasm Proteins
  • Transfection
Sprache
eng
Country
England
Paginierung
238 - 245
PII
dkl474
Datum der Veröffentlichung
2007
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2007
Titel
Modulation of human BCRP (ABCG2) activity by anti-HIV drugs.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
59

Data source: PubMed

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