Rifampicin and rifabutin can activate the pregnane X receptor (PXR, NR1I2 ), thereby inducing pharmacokinetically important genes/proteins and reducing exposure to co-administered drugs. Because induction effects vary considerably between these antibiotics, differences could be due to unequal rifamycin-induced activation or tissue expression of the three major NR1I2 splice variants, PXR.1 (NM_003889), PXR.2 (NM_022002), and PX...

Compared to rifampicin (600 mg/day), standard doses of rifabutin (300 mg/day) have a lower risk of drug–drug interactions due to induction of cytochrome P450 3A4 (CYP3A4) or P-glycoprotein (Pgp/ ABCB1 ) mediated by the pregnane X receptor (PXR). However, clinical comparisons with equal rifamycin doses or in vitro experiments respecting actual intracellular concentrations are lacking. Thus, the genuine pharmacological differenc...

The activity of nuclear receptors (e.g., pregnane x receptor, PXR) can be assessed by luminescence-based dual reporter gene assays. Under most conditions, receptor-activated firefly luminescence is normalized to Renilla luminescence, which is triggered by a constitutively active promoter. Simultaneous damage to the cells can however disrupt these signals and thus impair the interpretation of the data. Consequently, this study...