Fluoroquinolone antibiotics inhibit cytochrome P450-mediated microsomal drug metabolism in rat and human.
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McLellan RA, Drobitch RK, Monshouwer M, Renton KW
Fluoroquinolone antibiotics inhibit cytochrome P450-mediated microsomal drug metabolism in rat and human.
Drug Metab Dispos. 1996 Oct;24(10):1134-8.
- PubMed ID
- 8894516 [ View in PubMed]
- Abstract
The fluoroquinolone antibacterial agents have gained widespread use in the treatment of a broad range of bacterial infections. We recently described a possible interaction concerning the concomitant use of cyclosporine A and norfloxacin in pediatric renal transplant patients. We examined the effect of two common fluoroquinolone antibiotics on cytochrome P450-mediated drug biotransformations in human and rat liver microsomes. Rats were pretreated with inducers, which increased the levels of the P450 isozymes CYP3A2, CYP1A, CYP2E1, and CYP4A1. Ciprofloxacin and norfloxacin significantly depressed the N-demethylation of erythromycin by CYP3A4 in human microsomes and by CYP3A2 in rat microsomes. The inhibition was determined to be competitive in nature in rat microsomes, with ciprofloxacin and norfloxacin both exhibiting similar Ki values of 2.0 and 2.3 mM, respectively. Ciprofloxacin and norfloxacin also inhibited ethoxyresorufin-O-dealkylase (CYP1A). In contrast, ciprofloxacin and norfloxacin did not inhibit the metabolism of substrates that are specific for the P450 isozymes CYP2E1 and CYP4A1. Rats treated chronically with norfloxacin revealed no alterations in hepatic CYP3A2 protein levels or activity. These studies in hepatic microsomes demonstrate that fluoroquinolones can decrease CYP3A- and CYP1A-mediated biotransformation by competitive inhibition and that they have the potential to cause drug interactions with agents metabolized by these enzymes.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Ciprofloxacin Cytochrome P450 3A4 Protein Humans UnknownInhibitorDetails Norfloxacin Cytochrome P450 1A1 Protein Humans UnknownInhibitorDetails Norfloxacin Cytochrome P450 3A4 Protein Humans UnknownInhibitorDetails Norfloxacin Cytochrome P450 3A7 Protein Humans NoInhibitorDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareAminophyllineEnoxacin The metabolism of Aminophylline can be decreased when combined with Enoxacin. AminophyllineTechnetium Tc-99m ciprofloxacin The metabolism of Aminophylline can be decreased when combined with Technetium Tc-99m ciprofloxacin. AminophyllineMoxifloxacin The metabolism of Aminophylline can be decreased when combined with Moxifloxacin. AminophyllineGatifloxacin The metabolism of Aminophylline can be decreased when combined with Gatifloxacin. AminophyllinePazufloxacin The metabolism of Aminophylline can be decreased when combined with Pazufloxacin.