Differential inhibition of human CYP1A1 AND CYP1A2 by quinidine and quinine.

Wang, S. M., Blake, C. L., Malek, N. A., Angus, P. W. and Ghabrial, H. (2001) Differential inhibition of human CYP1A1 AND CYP1A2 by quinidine and quinine.. Xenobiotica, 31 11: 757-767. doi:10.1080/00498250110065603


Author Wang, S. M.
Blake, C. L.
Malek, N. A.
Angus, P. W.
Ghabrial, H.
Title Differential inhibition of human CYP1A1 AND CYP1A2 by quinidine and quinine.
Journal name Xenobiotica   Check publisher's open access policy
ISSN 1366-5928
Publication date 2001-01-01
Sub-type Article (original research)
DOI 10.1080/00498250110065603
Open Access Status Not yet assessed
Volume 31
Issue 11
Start page 757
End page 767
Total pages 11
Place of publication UK
Publisher Taylor & Francis
Language eng
Subject CX
320501 Pharmaceutical Sciences and Pharmacy
670403 Treatments (e.g. chemicals, antibiotics)
Abstract The inhibition of recombinant CYP1A1 and CYP1A2 activity by quinidine and quinine was evluated using ethoxyresorufin O -deethylation, phenacetin O -deethylation and propranolol desisopropylation as probe catalytic pathways. 2. With substrate concentrations near the K m of catalysis, both quinidine and quinine potently inhibited CYP1A1 activity with [ I ] 0.5 ~ 1-3 μM, whereas in contrast, there was little inhibition of CYP1A2 activity. The Lineweaver-Burk plots with varying inhibitor concentrations suggested that inhibition by quinidine and quinine was competitive. 3. There was only trace metabolism of quinidine by recombinant CYP1A1, whereas rat liver microsomes as a control showed extensive consumption of quinidine and metabolite production. 4. This work suggests that quinidine is a non-classical inhibitor of CYP1A1 and that it is not as highly specific at inhibiting CYP2D6 as previously thought.
Keyword Pharmacology
Toxicology
Q-Index Code CX

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
 
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Created: Wed, 15 Aug 2007, 01:43:21 EST