alexa Rifampin is a selective, pleiotropic inducer of drug metabolism genes in human hepatocytes: studies with cDNA and oligonucleotide expression arrays.
Microbiology

Microbiology

Mycobacterial Diseases

Author(s): Rae JM, Johnson MD, Lippman ME, Flockhart DA

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Abstract We used expression microarrays to test the effects of rifampin on the overall pattern of mRNA expression of multiple metabolic enzymes in primary human hepatocytes. Two microarrays were utilized, a cDNA-based array and one that is oligonucleotide-based. The cDNA-based expression arrays showed that rifampin caused a 7.7 +/- 6.6-fold induction in CYP2A6 and a 4.0 +/- 2.0-fold increase in the CYP2C family of enzymes while having little effect on CYP2E1 or CYP2D6. Many non-P450 enzymes were also induced including FMO-4 and -5, UGT-1A, MAO-B, and GST-P1. The oligonucleotide-based array made it possible to detect different levels of induction within the CYP2C family, with rifampin causing a 6.5-fold increase in expression of CYP2C8 and a 3.7-fold increase in CYP2C9 while having no effect on the level of CYP2C18 mRNA. Rifampin also induced other CYP enzymes including CYP2B6 and all three members of the CYP3A family, with CYP3A4 showing the highest level of induction at 55.1-fold. RNase protection assays were used to validate results from the arrays and a comparison of all three methods of mRNA detection showed qualitatively similar results. These data make it clear that rifampin treatment brings about broad changes in the pattern of gene expression, rather than increased expression of a small number of metabolic enzymes. Clinicians and researchers who use and study rifampin and other drugs that induce drug metabolism should be alert to the possibility of multiple effects.
This article was published in J Pharmacol Exp Ther and referenced in Mycobacterial Diseases

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