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Polymorphic Hydroxylation of Perhexiline in Vitro by L. B. Sørensen; R. N. Sørensen; J. O. Miners; A. A. Somogyi; N. Grgurinovich; D. J. Birkett is a Medicine article available to read on EtoBox.
What is Polymorphic Hydroxylation of Perhexiline in Vitro about?
Aims The aims of this study were to examine the __in vitro__ enzyme kinetics and CYP isoform selectivity of perhexiline monohydroxylation using human liver microsomes. Methods Conversion of rac‐perhexiline to monohydroxyperhexiline by human liver microsomes was assessed using a high‐performance liquid chromatography assay with precolumn derivatization to measure the formation rate of the product. Isoform selective inhibitors were used to define the CYP isoform profile of perhexiline monohydroxylation. Results The rate of perhexiline monohydroxylation with microsomes from 20 livers varied 50‐fold. The activity in 18 phenotypic perhexiline extensive metabolizer (PEM) livers varied about five‐fold. The apparent K~m~ was 3.3 ± 1.5 μm, the __V__~max~ was 9.1 ± 3.1 pmol min^−1^ mg^−1^ microsomal protein and the __in vitro__ intrinsic clearance (__V__~max~/K~m~) was 2.9 ± 0.5 μl min^−1^ mg^−1^ microsomal protein in the extensive metabolizer livers. The corresponding values in the poor metabolizer livers were: apparent K~m~ 124 ± 141 μm; __V__~max~ 1.4 ± 0.6 pmol min^−1^ mg^−1^ microsomal protein; and intrinsic clearance 0.026 μl min^−1^ mg^−1^ microsomal protein. Quinidine almost compl
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- Author
- L. B. Sørensen; R. N. Sørensen; J. O. Miners; A. A. Somogyi; N. Grgurinovich; D. J. Birkett
- Publisher
- John Wiley and Sons; Wiley (Blackwell Publishing); Blackwell Publishing Inc.; Wiley; Research Square (ISSN 0306-5251)
- Published
- 2003
- Language
- EN
- Field
- Medicine (Health Sciences)