iP-gp , a novel cell line with tight barrier function and expression of human P-glycoprotein (ABCB1) for drug screening

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Standard

iP-gp , a novel cell line with tight barrier function and expression of human P-glycoprotein (ABCB1) for drug screening. / Brodin, Birger; Ozgür, Burak; Saaby, Lasse.

2017. Abstract from 6th FIP Pharmaceutical Sciences World Congress 2017., Stockholm, Sweden.

Research output: Contribution to conferenceConference abstract for conferenceResearchpeer-review

Harvard

Brodin, B, Ozgür, B & Saaby, L 2017, 'iP-gp , a novel cell line with tight barrier function and expression of human P-glycoprotein (ABCB1) for drug screening', 6th FIP Pharmaceutical Sciences World Congress 2017., Stockholm, Sweden, 21/05/2017 - 24/05/2017. <https://fip.org/abstracts?page=abstracts&action=item&item=18382>

APA

Brodin, B., Ozgür, B., & Saaby, L. (2017). iP-gp , a novel cell line with tight barrier function and expression of human P-glycoprotein (ABCB1) for drug screening. Abstract from 6th FIP Pharmaceutical Sciences World Congress 2017., Stockholm, Sweden. https://fip.org/abstracts?page=abstracts&action=item&item=18382

Vancouver

Brodin B, Ozgür B, Saaby L. iP-gp , a novel cell line with tight barrier function and expression of human P-glycoprotein (ABCB1) for drug screening. 2017. Abstract from 6th FIP Pharmaceutical Sciences World Congress 2017., Stockholm, Sweden.

Author

Brodin, Birger ; Ozgür, Burak ; Saaby, Lasse. / iP-gp , a novel cell line with tight barrier function and expression of human P-glycoprotein (ABCB1) for drug screening. Abstract from 6th FIP Pharmaceutical Sciences World Congress 2017., Stockholm, Sweden.

Bibtex

@conference{ea2ac3635f8b47aba4adc7294a23660a,
title = "iP-gp , a novel cell line with tight barrier function and expression of human P-glycoprotein (ABCB1) for drug screening",
abstract = "Background: The efflux transporter P-glycoprotein (P-gp, product of the MDR1/ABCB1 gene) hindersuptake of drug compounds to the brain, limits intestinal uptake, is a cause of resistance to chemoterapeutics and a potential {"}site{"} for drug-drug interaction. Regulatory agencies therefore recommend that new API's are evaluated with respect to P-gp interactions. Aim: The aim of the present work was to validate the suitability of the newly developed iP-gp cell line for investigating P-gp interactions with human P-gp.Methods: IPEC-J2 MDR1 (iP-gp) cells were cultured on permeable supports for 17-20 days in conventional growth media. Results: The iP-gp cell line generated tight monolayers after 16 days of culture (TEER > 15000 ohm·cm2). Efflux ratios (Papp, B-A / Papp, A-B) of the P-gp substrate digoxin were in the range of 80-100. P-gp was demonstrated to be responsible for the efflux transport by substrate profiling, combined with application of P-gp and BCRP inhibitors. Furthermore, the compounds atenolol, citalopram, and mitoxantrone were identified as P-gp substrates. Functional P-gp expression was shown to be stable through at least 10 cell passages.Transport kinetic analysis of rhodamine and digoxin B-A fluxes revealed that rhodamine 123 had a Km and Vmax of 332µM +/- 124 µM and 111 +/- 16 pmol·cm-2·min-1, respectively. Vmax and Km of digoxin transport could not be estimated due to the low solubility of digoxin. The IC50 of the inhibitor, zosuquidar, were estimated to 0.05 +/- 0.01 µM and 0.04 +/- 0.01 µM in transport experiments including digoxin and rhodamine 123, respectively. Summary/Conclusion: The iP-gp cell line may become a useful screening tool for interactions between drug compounds and human P-gp.",
author = "Birger Brodin and Burak Ozg{\"u}r and Lasse Saaby",
year = "2017",
month = may,
day = "23",
language = "English",
note = "6th FIP Pharmaceutical Sciences World Congress 2017. ; Conference date: 21-05-2017 Through 24-05-2017",

}

RIS

TY - ABST

T1 - iP-gp , a novel cell line with tight barrier function and expression of human P-glycoprotein (ABCB1) for drug screening

AU - Brodin, Birger

AU - Ozgür, Burak

AU - Saaby, Lasse

PY - 2017/5/23

Y1 - 2017/5/23

N2 - Background: The efflux transporter P-glycoprotein (P-gp, product of the MDR1/ABCB1 gene) hindersuptake of drug compounds to the brain, limits intestinal uptake, is a cause of resistance to chemoterapeutics and a potential "site" for drug-drug interaction. Regulatory agencies therefore recommend that new API's are evaluated with respect to P-gp interactions. Aim: The aim of the present work was to validate the suitability of the newly developed iP-gp cell line for investigating P-gp interactions with human P-gp.Methods: IPEC-J2 MDR1 (iP-gp) cells were cultured on permeable supports for 17-20 days in conventional growth media. Results: The iP-gp cell line generated tight monolayers after 16 days of culture (TEER > 15000 ohm·cm2). Efflux ratios (Papp, B-A / Papp, A-B) of the P-gp substrate digoxin were in the range of 80-100. P-gp was demonstrated to be responsible for the efflux transport by substrate profiling, combined with application of P-gp and BCRP inhibitors. Furthermore, the compounds atenolol, citalopram, and mitoxantrone were identified as P-gp substrates. Functional P-gp expression was shown to be stable through at least 10 cell passages.Transport kinetic analysis of rhodamine and digoxin B-A fluxes revealed that rhodamine 123 had a Km and Vmax of 332µM +/- 124 µM and 111 +/- 16 pmol·cm-2·min-1, respectively. Vmax and Km of digoxin transport could not be estimated due to the low solubility of digoxin. The IC50 of the inhibitor, zosuquidar, were estimated to 0.05 +/- 0.01 µM and 0.04 +/- 0.01 µM in transport experiments including digoxin and rhodamine 123, respectively. Summary/Conclusion: The iP-gp cell line may become a useful screening tool for interactions between drug compounds and human P-gp.

AB - Background: The efflux transporter P-glycoprotein (P-gp, product of the MDR1/ABCB1 gene) hindersuptake of drug compounds to the brain, limits intestinal uptake, is a cause of resistance to chemoterapeutics and a potential "site" for drug-drug interaction. Regulatory agencies therefore recommend that new API's are evaluated with respect to P-gp interactions. Aim: The aim of the present work was to validate the suitability of the newly developed iP-gp cell line for investigating P-gp interactions with human P-gp.Methods: IPEC-J2 MDR1 (iP-gp) cells were cultured on permeable supports for 17-20 days in conventional growth media. Results: The iP-gp cell line generated tight monolayers after 16 days of culture (TEER > 15000 ohm·cm2). Efflux ratios (Papp, B-A / Papp, A-B) of the P-gp substrate digoxin were in the range of 80-100. P-gp was demonstrated to be responsible for the efflux transport by substrate profiling, combined with application of P-gp and BCRP inhibitors. Furthermore, the compounds atenolol, citalopram, and mitoxantrone were identified as P-gp substrates. Functional P-gp expression was shown to be stable through at least 10 cell passages.Transport kinetic analysis of rhodamine and digoxin B-A fluxes revealed that rhodamine 123 had a Km and Vmax of 332µM +/- 124 µM and 111 +/- 16 pmol·cm-2·min-1, respectively. Vmax and Km of digoxin transport could not be estimated due to the low solubility of digoxin. The IC50 of the inhibitor, zosuquidar, were estimated to 0.05 +/- 0.01 µM and 0.04 +/- 0.01 µM in transport experiments including digoxin and rhodamine 123, respectively. Summary/Conclusion: The iP-gp cell line may become a useful screening tool for interactions between drug compounds and human P-gp.

M3 - Conference abstract for conference

T2 - 6th FIP Pharmaceutical Sciences World Congress 2017.

Y2 - 21 May 2017 through 24 May 2017

ER -

ID: 195587741