Blood-brain barrier transport of H1-antagonist ebastine and its metabolite carebastine

Journal of Drug Targeting
I TamaiAkira Tsuji

Abstract

The transport mechanism of the non-sedative H1-antagonist ebastine and its first-pass carboxylic acid metabolite carebastine at the blood-brain barrier (BBB) was studied. In rats, the brain uptake index (BUI) value of [14 C]carebastine was significantly lower than that of [14 C]ebastine. The BUI value of [14 C]carebastine was greatly increased by the addition of non-labeled carebastine. The steady-state uptake of [14 C]carebastine by P-glycoprotein-overexpressing K562/ADM cells was significantly lower than that by their parental drug-sensitive cell line K562. The decreased steady-state uptake of [14 C]carebastine by K562/ADM cells was reversed by verapamil. Steady-state uptake of [14 C]carebastine by primary cultured bovine brain capillary endothelial cells (bovine BCECs) was increased in the presence of metabolic inhibitors and verapamil. Non-labeled carebastine increased the steady-state uptake of a P-glycoprotein substrate, [3 H]vincristine, by bovine BCECs. The initial uptake of [3 H]mepyramine by bovine BCECs and RBEC1 (an immortalized cell line from rat brain capillary endothelial cells) was strongly inhibited by ebastine, while zwitterionic carebastine was slightly inhibitory. The values of brain-to-plasma unbound concen...Continue Reading

References

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Citations

Jun 10, 2004·Biological & Pharmaceutical Bulletin·Yoshiaki MorikiJun Watanabe
Jan 4, 2003·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Akira Tsuji
Feb 18, 2005·NeuroRx : the Journal of the American Society for Experimental NeuroTherapeutics·Akira Tsuji
May 13, 2014·Neurochemistry International·Dong-Chan KimKyong-Tai Kim
Jun 19, 2004·Journal of Drug Targeting·Remigijus DidziapetrisAlanas Petrauskas
Jul 16, 2009·Drug Metabolism Reviews·Margherita Strolin BenedettiJean-Baptiste Watelet
Mar 30, 2012·Current Medical Research and Opinion·K YanaiR Boev
Jul 14, 2005·Progress in Neurobiology·Wolfgang Löscher, Heidrun Potschka
Aug 21, 2015·European Journal of Pharmacology·Yawen HuWalter H Hsu
May 1, 2008·Drug Metabolism and Pharmacokinetics·Nobuhito MimuraEiichi Fuse
Dec 25, 2004·Drug Metabolism and Pharmacokinetics·Akira Tsuji
Aug 22, 2007·Drug Metabolism and Drug Interactions·Thomas Broeng EjsingKristian Linnet
Feb 4, 2006·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Rikiya OhashiIkumi Tamai
Apr 22, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Naoki IshiguroIkumi Tamai
Sep 3, 2004·Drug Discovery Today·Yoshimichi Sai, Akira Tsuji
Aug 29, 2021·Pharmaceutics·Nayyer IslamMohammed A S Abourehab

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