| Cytochrome P450 isoform-specific in vitro methods to predict drug metabolism and interactions | ||
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The methods for seven P450 specific activities, the use of chemical and antibody inhibitors and some cDNA-expressed enzymes were characterised for use in routine low-throughput preclinical in vitro testing of NCEs in human liver microsomes.
These approaches were tested during this work for eleven different activities. The results from the different approaches were shown to be relevant, repeatable and reliable, and it is proposed that these methods are suitable for this kind of work.
Tranylcypromine was evaluated to be a selective chemical inhibitor for CYP2A6 in a certain concentration range under one micromolar level.
The results of each study have been discussed in separate publications in the light of the existing in vivo data. The in vitro results for the studied angiotensin II receptor antagonists are in line with the available in vivo data, but the participation of CYP3A4 in vivo in selegiline and entacapone metabolism remains to be clarified.