Inhibitory effect of antituberculosis drugs on human cytochrome P450-mediated activities.
Article Details
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Nishimura Y, Kurata N, Sakurai E, Yasuhara H
Inhibitory effect of antituberculosis drugs on human cytochrome P450-mediated activities.
J Pharmacol Sci. 2004 Nov;96(3):293-300. Epub 2004 Nov 5.
- PubMed ID
- 15528841 [ View in PubMed]
- Abstract
The potential for drug-drug interactions mediated by the inhibition of cytochrome P-450 (CYP) were concerned during antituberculosis therapy. However, the information regarding human CYP inhibition by antituberculosis drugs is limited to isoniazid. In the current study, we examined the inhibitory effects of pyrazinamide and ethionamide, both of which are chemically related to isoniazid, on the CYP-mediated activities in human liver microsomes and compared them to that of isoniazid. No remarkable effects on any CYP activities were observed by pyrazinamide and ethionamide. In contrast, in addition to the reported inhibitory effect of isoniazid on CYP1A2, CYP2A6, CYP2C19, and CYP3A activities, our results newly showed its effect on CYP2C9 and CYP2E1 activities. Isoniazid showed potent direct inhibitory effect on S-warfarin 7-hydroxylation, while a preincubation step in the presence of NADPH was needed to inhibit chlorzoxazone 6-hydroxylation. Furthermore, irreversible inhibition of CYP2C19 activity by isoniazid was also observed in the dilution study. These results suggested that pyrazinamide and ethionamide did not seem to cause drug interactions mediated by the inhibition of CYP. In contrast, isoniazid might contribute to the severe drug interactions by a different inhibitory mechanism depending on each of the CYP isozymes, in addition to the reported observations.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Isoniazid Cytochrome P450 2A6 Protein Humans UnknownInhibitorDetails Isoniazid Cytochrome P450 2C19 Protein Humans UnknownInhibitorDetails Isoniazid Cytochrome P450 2C9 Protein Humans UnknownInhibitorDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareAminophyllineIsoniazid The serum concentration of Aminophylline can be increased when it is combined with Isoniazid. BromotheophyllineIsoniazid The serum concentration of Bromotheophylline can be increased when it is combined with Isoniazid. CaffeineIsoniazid The serum concentration of Caffeine can be increased when it is combined with Isoniazid. DyphyllineIsoniazid The serum concentration of Dyphylline can be increased when it is combined with Isoniazid. LomifyllineIsoniazid The serum concentration of Lomifylline can be increased when it is combined with Isoniazid.