Blog
About

1
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      In vitro metabolism of alectinib, a novel potent ALK inhibitor, in human: contribution of CYP3A enzymes.

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          1. The in vitro metabolism of alectinib, a potent and highly selective oral anaplastic lymphoma kinase inhibitor, was investigated. 2. The main metabolite (M4) in primary human hepatocytes was identified, which is produced by deethylation at the morpholine ring. Three minor metabolites (M6, M1a, and M1b) were also identified, and a minor peak of hydroxylated alectinib (M5) was detected as a possible precursor of M4, M1a, and M1b. 3. M4, an important active major metabolite, was produced and further metabolized to M6 by CYP3A, indicating that CYP3A enzymes were the principal contributors to this route. M5 is possibly produced by CYP3A and other isoforms as the primary step in metabolism, followed by oxidation to M4 mainly by CYP3A. Alternatively, M5 could be oxidized to M1a and M1b via an NAD-dependent process. None of the non-CYP3A-mediated metabolism appeared to be major. 4. In conclusion, this study suggests that involvement of multiple enzymes in the metabolism of alectinib reduces its potential for drug-drug interactions.

          Related collections

          Author and article information

          Journal
          Xenobiotica
          Xenobiotica; the fate of foreign compounds in biological systems
          Informa UK Limited
          1366-5928
          0049-8254
          Jun 2018
          : 48
          : 6
          Affiliations
          [1 ] a Chugai Pharmaceutical Co. Ltd ., Gotemba , Japan.
          [2 ] b Non-Clinical Drug Safety, F. Hoffmann-La Roche Ltd. , Basel , Switzerland.
          [3 ] c Roche Innovation Center , New York , NY , USA.
          Article
          10.1080/00498254.2017.1344910
          28657423

          Comments

          Comment on this article