Carebastine-d5 is intended for use as an internal standard for the quantification of carebastine by GC- or LC-MS. Carebastine is an active metabolite of ebastine .1,2 Ebastine undergoes extensive first-pass metabolism by the hepatic cytochrome P450 (CYP) isomer CYP3A4 into carebastine, which acts as an antagonist at histamine H1 receptors (IC50 = 45 nM).2,3 Carebastine decreases production of RANTES/CCL5 and monocyte chemoattractant protein 1 (MCP-1/CCL2) in human nasal epithelial cells (HNECs) isolated from patients with nasal allergies.4
1.Vincent, J., Liminana, R., Meredith, P.A., et al.The pharmacokinetics, antihistamine and concentration-effect relationship of ebastine in healthy subjectsBr. J. Clin. Pharmacol.26(5)497-502(1988) 2.Liu, K.-H., Kim, M.-G., Lee, D.-J., et al.Characterization of ebastine, hydroxyebastine, and carebastine metabolism by human liver microsomes and expressed cytochrome P450 enzymes: Major roles for CYP2J2 and CYP3ADrug. Metab. Dispos.34(11)1793-1797(2006) 3.Abou-Gharbia, M., Moyer, J.A., Nielsen, S.T., et al.New antihistamines: Substituted piperazine and piperidine derivatives as novel H1-antagonistsJ. Med. Chem.38(20)4026-4032(1995) 4.Yamauchi, Y., Fujikura, T., and Shimosawa, T.The effect of H1 antagonists carebastine and olopatadine on histamine induced expression of CC chemokines in cultured human nasal epithelial cellsAllergol. Int.56(2)171-177(2007)