Substrate stereoselectivity and enantiomer/enantiomer interaction in propranolol metabolism in rat liver microsomes

Yasuhiro Masubuchi, Luis Aquira Yamamoto, Mineko Uesaka, Shoichi Fujita, Shizuo Narimatsu, Tokuji Suzuki

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The substrate stereoselectivity and enantiomer/enantiomer interaction of (S)- and (R)-propranolol for the formation of their metabolites were investigated in rat liver microsomal fractions. The enantiomers of primary metabolites of propranolol, 4-, 5-, 7-hydroxy- and N-desisopropylpropranolol were separated and assayed by an HPLC method employing a chiral ovomucoid column. Regioselective substrate stereoselectivity (R < S for 4- and 5-hydroxylations; R > S for - 7-hydroxylation; R = S for N-desisopropylation) was observed in the formation of propranolol metabolites when the individual enantiomers or a racemic mixture of propranolol were used as substrates. Concentration-dependent metabolic inhibition of propranolol enantiomers by their optical isomers was also observed. In addition, the inhibition of propranolol 4-, 5- and 7-hydroxylations between the enantiomers showed a typical competitive nature. These findings suggested that the propranolol enantiomers competed for the same enzyme, probably a cytochrome P450 isozyme in the CYP2D subfamily.

Original languageEnglish
Pages (from-to)1759-1765
Number of pages7
JournalBiochemical Pharmacology
Issue number10
Publication statusPublished - Nov 17 1993


ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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