An S-warfarin and AZD1981 interaction: in vitro and clinical pilot data suggest the N-deacetylated amino acid metabolite as the primary perpetrator
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- 作者：Ken Grime ; Rikard Pehrson ; Pä ; r Nordell ; Michael Gillen ; Wolfgang Kü ; hn ; Timothy Mant ; Marie Brä ; nnströ ; m ; Petter Svanberg ; Barry Jones and Clive Brealey
- 刊名：British Journal of Clinical Pharmacology
- 出版年：2017
- 出版时间：February 2017
- 年：2017
- 卷：83
- 期：2
- 页码：381-392
- 全文大小：897K
- ISSN：1365-2125
文摘
AZD1981 is an orally bioavailable chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTh2) receptor antagonist progressed to phase II trials for the treatment of allergic asthma. Previously performed in vitro human hepatocyte incubations identified N-deacetylated AZD1981 as a primary metabolite. We report on metabolite exposure from a clinical excretion balance, on in vitro studies performed to determine the likelihood of a metabolite-dependent drug–drug interaction (DDI) and on a clinical warfarin DDI study. The aim was to demonstrate that N-deacetylated AZD1981 is responsible for the observed interaction.