Cytochrome P4502C9: an enzyme of major importance in human drug metabolism.

Article Details

Citation

Miners JO, Birkett DJ

Cytochrome P4502C9: an enzyme of major importance in human drug metabolism.

Br J Clin Pharmacol. 1998 Jun;45(6):525-38.

PubMed ID
9663807 [ View in PubMed
]
Abstract

Accumulating evidence indicates that CYP2C9 ranks amongst the most important drug metabolizing enzymes in humans. Substrates for CYP2C9 include fluoxetine, losartan, phenytoin, tolbutamide, torsemide, S-warfarin, and numerous NSAIDs. CYP2C9 activity in vivo is inducible by rifampicin. Evidence suggests that CYP2C9 substrates may also be induced variably by carbamazepine, ethanol and phenobarbitone. Apart from the mutual competitive inhibition which may occur between alternate substrates, numerous other drugs have been shown to inhibit CYP2C9 activity in vivo and/or in vitro. Clinically significant inhibition may occur with coadministration of amiodarone, fluconazole, phenylbutazone, sulphinpyrazone, sulphaphenazole and certain other sulphonamides. Polymorphisms in the coding region of the CYP2C9 gene produce variants at amino acid residues 144 (Arg144Cys) and 359 (Ile359Leu) of the CYP2C9 protein. Individuals homozygous for Leu359 have markedly diminished metabolic capacities for most CYP2C9 substrates, although the frequency of this allele is relatively low. Consistent with the modulation of enzyme activity by genetic and other factors, wide interindividual variability occurs in the elimination and/or dosage requirements of prototypic CYP2C9 substrates. Individualisation of dose is essential for those CYP2C9 substrates with a narrow therapeutic index.

DrugBank Data that Cites this Article

Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
ClotrimazoleCytochrome P450 2C9ProteinHumans
Unknown
Inhibitor
Details
PhenylbutazoneCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Inhibitor
Details
SecobarbitalCytochrome P450 2C9ProteinHumans
Unknown
Inducer
Details
SeratrodastCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
SulfamethoxazoleCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Inhibitor
Details
TenoxicamCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
Drug Interactions
DrugsInteraction
Fosphenytoin
Tolbutamide
The serum concentration of Fosphenytoin can be increased when it is combined with Tolbutamide.
Phenytoin
Tolbutamide
The serum concentration of Phenytoin can be increased when it is combined with Tolbutamide.
Interactions
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