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Titolo:
Rifampin is a selective, pleiotropic inducer of drug metabolism genes in human hepatocytes: Studies with cDNA and oligonucleotide expression arrays
Autore:
Rae, JM; Johnson, MD; Lippman, ME; Flockhart, DA;
Indirizzi:
Georgetown Univ, Med Ctr, Dept Pharmacol, Washington, DC 20007 USA Georgetown Univ Washington DC USA 20007 armacol, Washington, DC 20007 USA Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20007 USA Georgetown Univ Washington DC USA 20007 t Oncol, Washington, DC 20007 USA Georgetown Univ, Med Ctr, Dept Med, Div Clin Pharmacol, Washington, DC 20007 USA Georgetown Univ Washington DC USA 20007 armacol, Washington, DC 20007 USA
Titolo Testata:
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
fascicolo: 3, volume: 299, anno: 2001,
pagine: 849 - 857
SICI:
0022-3565(200112)299:3<849:RIASPI>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
POLYMERASE CHAIN-REACTION; NUCLEAR RECEPTORS; PRIMARY CULTURES; MESSENGER-RNA; CYTOCHROME-P450 INDUCTION; ENHANCER MODULE; ACTIVATION; CYP3A4; CAR; ENZYMES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
35
Recensione:
Indirizzi per estratti:
Indirizzo: Rae, JM Univ Michigan, Dept Internal Med, Room 5312,1500 E Med Ctr Dr, AnnArbor, MI 48109 USA Univ Michigan Room 5312,1500 E Med Ctr Dr Ann Arbor MIUSA 48109 A
Citazione:
J.M. Rae et al., "Rifampin is a selective, pleiotropic inducer of drug metabolism genes in human hepatocytes: Studies with cDNA and oligonucleotide expression arrays", J PHARM EXP, 299(3), 2001, pp. 849-857

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-foldincrease 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 CYP2136 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 thearrays and a comparison of all three methods of mRNA detection showed qualitatively similar results. These data make it clear that rifampin treatmentbrings about broad changes in the pattern of gene expression, rather than increased expression of a small number of metabolic enzymes. Clinicians andresearchers who use and study rifampin and other drugs that induce drug metabolism should be alert to the possibility of multiple effects.

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Documento generato il 23/01/20 alle ore 03:55:22