The pyrazolone drug metamizole is a widely used analgesic. Analysis of liver microsomes from patients treated with metamizole revealed selectively higher expression of cytochromes P450, CYP2B6 and CYP3A4 (3.8‐ and 2.8‐fold, respectively), and 2.9‐fold higher bupropion hydroxylase activity compared with untreated subjects. Further investigation of metamizole and various derivatives on different potential target genes in human primary hepatocytes demonstrated time‐ and concentration‐dependent induction by metamizole of CYP2B6 (7.8‐ and 3.1‐fold for mRNA and protein, respectively, at 100 μM) and CYP3A4 (2.4‐ and 2.9‐fold, respectively), whereas other genes (CYP2C9, CYP2C19, CYP2D6, NADPH:cytochrome P450 reductase, ABCB1, constitutive androstane receptor (CAR), pregnane X receptor (PXR)) were not substantially altered. Using reporter gene assays, we show that metamizole is not acting as a direct ligand to either PXR or CAR, suggesting a phenobarbital‐like mechanism of induction. These data warrant further studies to elucidate the drug‐interaction potential of metamizole, especially in patients with long‐term treatment.

Clinical Pharmacology & Therapeutics (2007) 82, 265–274; doi:10.1038/sj.clpt.6100138; published online 7 March 2007