Title : Does metronidazole interact with CYP3A substrates by inhibiting their metabolism through this metabolic pathway? Or should other mechanisms be considered?

Pub. Date : 2007 Apr

PMID : 17374625






9 Functional Relationships(s)
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1 Does metronidazole interact with CYP3A substrates by inhibiting their metabolism through this metabolic pathway? Metronidazole cytochrome P450 family 3 subfamily A member 4 Homo sapiens
2 OBJECTIVE: To explore whether CYP3A inhibition by metronidazole is the primary mechanism by which metronidazole interacts with coadministered CYP3A substrates. Metronidazole cytochrome P450 family 3 subfamily A member 4 Homo sapiens
3 OBJECTIVE: To explore whether CYP3A inhibition by metronidazole is the primary mechanism by which metronidazole interacts with coadministered CYP3A substrates. Metronidazole cytochrome P450 family 3 subfamily A member 4 Homo sapiens
4 OBJECTIVE: To explore whether CYP3A inhibition by metronidazole is the primary mechanism by which metronidazole interacts with coadministered CYP3A substrates. Metronidazole cytochrome P450 family 3 subfamily A member 4 Homo sapiens
5 OBJECTIVE: To explore whether CYP3A inhibition by metronidazole is the primary mechanism by which metronidazole interacts with coadministered CYP3A substrates. Metronidazole cytochrome P450 family 3 subfamily A member 4 Homo sapiens
6 DATA SYNTHESIS: Elevated plasma concentrations and toxicities have been reported for a number of CYP3A substrates including amiodarone, carbamazepine, quinidine, tacrolimus, and cyclosporine when administered with metronidazole. Metronidazole cytochrome P450 family 3 subfamily A member 4 Homo sapiens
7 This has led to the widespread belief that metronidazole is a significant inhibitor of CYP3A4. Metronidazole cytochrome P450 family 3 subfamily A member 4 Homo sapiens
8 CONCLUSIONS: Drug interactions between metronidazole and certain CYP3A substrates do not appear to result from CYP3A4/5 inhibition by metronidazole. Metronidazole cytochrome P450 family 3 subfamily A member 4 Homo sapiens
9 Until any mechanism is identified by which metronidazole alters the disposition of certain CYP3A substrates, drug interactions with this agent should be assessed on a case-by-case basis, taking into account the safety index of the coadministered drug and the availability of equally effective substitutes for either metronidazole or the drug with which it putatively interacts. Metronidazole cytochrome P450 family 3 subfamily A member 4 Homo sapiens