Role of the multidrug transporter proteins ABCB1 and ABCC2 in the diaplacental transport of talinolol in the term human placenta

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Karen MayWerner Siegmund

Abstract

Placental syncytiotrophoblasts are known to express the efflux transporter proteins P-glycoprotein (ABCB1) and multidrug resistance-associated protein 2 (ABCC2), which are supposed to be a functional part of the human placental barrier. With advancing gestational age, expression of ABCB1 decreases progressively, whereas ABCC2 is more expressed. To evaluate to which extent they contribute to placental barrier function at term, permeability of talinolol, a substrate of both carriers, was measured using a validated human placenta perfusion model. We identified in randomized, crossover experiments a unidirectional transfer of talinolol in the fetomaternal direction because the maternofetal transfer was significantly lower (0.663 +/- 0.188 versus 0.394 +/- 0.067 relative to creatinine permeability, p = 0.012). Maternofetal permeability was increased by the ABCC2 inhibitor probenecid (0.59 +/- 0.15 versus 0.68 +/- 0.13, p = 0.028) and the nonspecific inhibitor verapamil (0.53 +/- 0.09 versus 0.66 +/- 0.16, p = 0.028) but was not influenced by the ABCB1 inhibitor valspodar (PSC833) (0.48 +/- 0.11 versus 0.46 +/- 0.09, p = 0.345). Genetic polymorphisms of ABCB1 and ABCC2 lacked significant influence on expression of the carriers and pe...Continue Reading

References

Nov 15, 1972·American Journal of Obstetrics and Gynecology·H SchneiderJ Dancis
Oct 8, 1999·Clinical Pharmacology and Therapeutics·T Gramatté, R Oertel
Feb 5, 2000·European Journal of Obstetrics, Gynecology, and Reproductive Biology·L A MageeG Koren
Mar 11, 2000·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·P BrownbillC P Sibley
Sep 27, 2000·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·M V St-PierreJ J Marin
Nov 14, 2000·The American Journal of Pathology·M F FrommD Schrenk
Jan 18, 2002·Antimicrobial Agents and Chemotherapy·Kazumasa NaruhashiAkira Tsuji
Dec 25, 2002·European Journal of Pharmacology·Simon LowesNicholas L Simmons
Jul 16, 2003·European Journal of Obstetrics, Gynecology, and Reproductive Biology·Gershon HolcbergZvi Ben-Zvi
Apr 12, 2005·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Henriette E Meyer zu SchwabedissenHeyo K Kroemer
May 7, 2005·Biochemical Pharmacology·Tatiana NanovskayaMahmoud S Ahmed
May 21, 2005·Clinical Pharmacology and Therapeutics·Ute I SchwarzWilhelm Kirch
Aug 9, 2005·Clinical Pharmacology and Therapeutics·Catia Marzolini, Richard B Kim
Aug 9, 2005·Clinical Pharmacology and Therapeutics·Melissa MölsäKari Laine
Mar 28, 2006·Reproductive Toxicology·Martina Ceckova-NovotnaFrantisek Staud
Apr 4, 2006·American Journal of Obstetrics and Gynecology·Jennifer KraemerGideon Koren
May 13, 2006·Current Opinion in Pharmacology·Szabolcs ModokRichard Callaghan
Jul 26, 2006·Expert Opinion on Drug Metabolism & Toxicology·Gabriele JedlitschkyHeyo K Kroemer
Jul 26, 2006·Expert Opinion on Drug Metabolism & Toxicology·Denis EvseenkoJeffrey A Keelan
Oct 6, 2006·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Markus GrubeHeyo K Kroemer
Oct 26, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jurjen S LagasAlfred H Schinkel
Jan 30, 2007·Journal of Psychopharmacology·Melissa RahiKari Laine
Jun 2, 2007·Expert Opinion on Drug Metabolism & Toxicology·Päivi MyllynenKirsi Vähäkangas
Jul 25, 2007·The Journal of Biological Chemistry·Thomas PerrottonHélène Baubichon-Cortay

❮ Previous
Next ❯

Citations

Nov 20, 2009·Archives of Gynecology and Obstetrics·Valeria FeinshteinZvi Ben-Zvi
Mar 31, 2012·Neural Development·Leigh E Wicki-StordeurLeigh Anne Swayne
May 5, 2012·PloS One·Gregory J AngerMicheline Piquette-Miller
May 20, 2009·Pharmacogenomics·Dalia Kasperaviciūte, Sanjay M Sisodiya
Sep 30, 2009·Expert Opinion on Drug Metabolism & Toxicology·Päivi MyllynenKirsi Vähäkangas
Jan 21, 2015·Expert Opinion on Drug Metabolism & Toxicology·Frantisek Staud, Martina Ceckova
Oct 1, 2009·British Journal of Pharmacology·Kirsi Vähäkangas, Päivi Myllynen
May 29, 2015·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Aizati N A DaudBob Wilffert
May 2, 2016·Reproductive Toxicology·Miriam Rubinchik-SternMichal Kovo
Aug 17, 2016·Advanced Drug Delivery Reviews·Sanaalarab Al-EnazyErik Rytting
Nov 4, 2016·Pharmaceutical Research·Anand A JoshiPhillip M Gerk
Oct 25, 2017·Pharmaceutics·Sarabjit S Gahir, Micheline Piquette-Miller
Mar 31, 2018·Scientific Reports·Leonie AengenheisterTina Buerki-Thurnherr

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antimicrobial Resistance (ASM)

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Antimicrobial Resistance

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.