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

Beth Williamson; Kelly E. Dooley; Yuan Zhang; David J. Back; Andrew Owen

doi:10.1128/AAC.01124-13

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

Beth Williamson, Kelly E. Dooley, Yuan Zhang, David J. Back, Andrew Owen

Research output: Contribution to journal › Article › peer-review

76 Scopus citations

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 aniontransporting 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.

Original language	English (US)
Pages (from-to)	6366-6369
Number of pages	4
Journal	Antimicrobial agents and chemotherapy
Volume	57
Issue number	12
DOIs	https://doi.org/10.1128/AAC.01124-13
State	Published - Dec 2013
Externally published	Yes

ASJC Scopus subject areas

Pharmacology
Pharmacology (medical)
Infectious Diseases

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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 aniontransporting 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.",

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AU - Williamson, Beth

AU - Dooley, Kelly E.

AU - Zhang, Yuan

AU - Back, David J.

AU - Owen, Andrew

PY - 2013/12

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AB - 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 aniontransporting 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.

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

Abstract

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