Involvement of CYP2D6 in Oxidative Metabolism of Cinnarizine and Flunarizine in Human Liver Microsomes

S. Narimatsu, S. Kariya, S. Isozaki, S. Ohmori, M. Kitada, S. Hosokawa, Y. Masubuchi, T. Suzuki

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Abstract

Oxidative metabolism of cinnarizine (CZ) and its fluorine derivative flunarizine (FZ), both of which are selective calcium entry blockers, was examined in human liver microsomes. The ring-hydroxylations and the N-desalkylations constituted primary metabolic pathways in microsomal metabolism of CZ and FZ. Among these pathways, the ring-hydroxylase (p-hydroxylation) activities at the cinnamyl moiety of both drugs were highly correlated with debrisoquine 4-hydroxylase activity and CYP2D6 content. Quinidine, a selective inhibitor of CYP2D6, suppressed the ring-hydroxylase activities of CZ and FZ. These results suggest that CYP2D6 is involved in the ring-hydroxylation of the cinnamyl moiety of both CZ and FZ in human liver microsomes.

Original languageEnglish
Pages (from-to)1262-1268
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume193
Issue number3
DOIs
Publication statusPublished - Jun 30 1993
Externally publishedYes

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ASJC Scopus subject areas

  • Molecular Biology
  • Biophysics
  • Biochemistry

Cite this

Narimatsu, S., Kariya, S., Isozaki, S., Ohmori, S., Kitada, M., Hosokawa, S., Masubuchi, Y., & Suzuki, T. (1993). Involvement of CYP2D6 in Oxidative Metabolism of Cinnarizine and Flunarizine in Human Liver Microsomes. Biochemical and Biophysical Research Communications, 193(3), 1262-1268. https://doi.org/10.1006/bbrc.1993.1761