title: Validation of quinidine as a probe substrate for the in vitro P-gp inhibition assay in Caco-2 cell monolayer.
abstract: Although quinidine has been recommended as a probe substrate for the P-gp inhibition assay using Caco-2 cell monolayer, it has not been studied widely in the in vitro system. In the present investigation, in vitro permeability studies using Caco-2 cell monolayer were carried out in order to optimize and validate quinidine as a P-gp probe substrate. In bi-directional Caco-2 assay across different passages, a good efflux ratio of more than ten was consistently obtained at 100 nM donor concentration of quinidine. Quinidine was found to have a good mass balance in the Caco-2 system. The inhibitory potencies of known P-gp inhibitors viz verapamil, ketoconazole, tacrolimus and cyclosporine A, determined over a wide concentration range, showed low apparent IC(50) values. Overall, quinidine was found to be a good probe substrate for routine use to assess the in vitro inhibitory potency of NCEs on Pgp-mediated transport.
authors: Drug Metabolism and Pharmacokinetics, Piramal Life Sciences Limited, Goregaon (E), Mumbai 400063, India.
authors: Anand G
authors: AG
authors: Patil
authors: Russell
authors: R
authors: D'Souza
authors: Neeta
authors: N
authors: Dixit
authors: Anagha
authors: A
authors: Damre
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000502:physiology; D001692:Biological Transport / Q000187:drug effects; D018938:Caco-2 Cells; D006801:Humans; D010539:Permeability; D011802:Quinidine / Q000494:pharmacology*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D011802:Quinidine