Ex Vivo Enzyme Induction
Studies of ex vivo induction in the rat, mouse, dog or monkey can provide valuable information to the investigation of a drug candidate. Not only are these types of induction studies cost-effective, they can provide the following information to your investigation:
- Which prototypical CYP inducers the drug candidate resembles
- Epigenetic tumor formation
- Which species most closely resembles human
- Drug-drug interactions
- Pharmacokinetic tolerance
- Increased elimination (auto-induction)
STUDY DETAILS
ASSAY SELECTION
CYP1A 7-Ethoxyresorufin O-dealkylation
CYP2A6 Coumarin 7-hydroxylation
CYP2B Resorufin O-dealkylation
CYP2B Testosterone oxidation
CYP2C Testosterone oxidation
CYP2D6 Dextromethorphan O-demethylation
CYP2E1 Chlorzoxazone 6-hydroxylation
CYP2E1 4-Nitrophenol hydroxylation
CYP3A Testosterone oxidation
CYP4A Lauric acid hydroxylation
Western blot analysis
TEST SYSTEM Microsomes prepared from treated tissue
INDUCERS b-naphthoflavone
phenobarbital
isoniazid
dexamethasone
rifampin
clofibric acid
AUTOMATION AND ANALYSIS Tecan liquid-handling system
Validated LC/MS/MS methods
High-throughput Shimadzu autosamplers
Deuterated internal standards
RELATED INFORMATION
FDA’s latest guidance document (PDF)