Induction of influx and efflux transporters and cytochrome P450 3A4 in primary human hepatocytes by rifampin, rifabutin, and rifapentine

Antimicrob Agents Chemother. 2013 Dec;57(12):6366-9. doi: 10.1128/AAC.01124-13. Epub 2013 Sep 23.

Abstract

Rifampin is a potent inducer of cytochrome P450 (CYP) enzymes and transporters. Drug-drug interactions during tuberculosis treatment are common. Induction by rifapentine and rifabutin is understudied. Rifampin and rifabutin significantly induced CYP3A4 (80-fold and 20-fold, respectively) in primary human hepatocytes. The induction was concentration dependent. Rifapentine induced CYP3A4 in hepatocytes from 3 of 6 donors. Data were also generated for ABCB1, ABCC1, ABCC2, organic anion-transporting polypeptide 1B1 (OATP1B1), and OATP1B3. This work serves as a basis for further study of the extent to which rifamycins induce key metabolism and transporter genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Cells, Cultured
  • Cytochrome P-450 CYP3A / metabolism
  • Hepatocytes / drug effects*
  • Hepatocytes / metabolism*
  • Humans
  • Membrane Transport Proteins / metabolism*
  • Multidrug Resistance-Associated Proteins / metabolism
  • Rifabutin / pharmacology*
  • Rifampin / analogs & derivatives*
  • Rifampin / pharmacology*

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Membrane Transport Proteins
  • Multidrug Resistance-Associated Proteins
  • Rifabutin
  • multidrug resistance-associated protein 2
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human
  • Rifampin
  • rifapentine
  • multidrug resistance-associated protein 1