Impact of the PXR-activator rifampicin on drug transporter gene expression in whole blood

Show full item record



Permalink

http://urn.fi/URN:NBN:fi:hulib-201606152425
Title: Impact of the PXR-activator rifampicin on drug transporter gene expression in whole blood
Author: Peled, Nitai
Other contributor: Helsingin yliopisto, Lääketieteellinen tiedekunta
University of Helsinki, Faculty of Medicine
Helsingfors universitet, Medicinska fakulteten
Publisher: Helsingfors universitet
Date: 2014
Language: eng
URI: http://urn.fi/URN:NBN:fi:hulib-201606152425
http://hdl.handle.net/10138/164153
Thesis level: master's thesis
Discipline: Clinical Pharmacology and Pharmacotherapy
Kliininen farmakologia ja lääkehoito
Klinisk farmakologi och läkemedelsbehandling
Abstract: Nitai Peled1, Miao Zefeng1, Tuija Tapaninen1,2, Pertti J. Neuvonen1,2 and Mikko Niemi1,2 1Department of Clinical Pharmacology, University of Helsinki, Finland 2HUSLAB, Helsinki University Central Hospital, Helsinki, Finland Rifampicin is a broad spectrum antibiotic used in the treatment of tuberculosis and staphylococcal infections. Through activation of pregnane X receptor (PXR), rifampicin induces the expression of several drug metabolizing enzymes and drug transporters. Previous studies suggest that rifampicin can induce the expression of certain drug transporters (e.g., ABCB1) in blood. Our aim was to investigate possible effects of rifampicin on drug transporter gene expression in whole blood. In a randomized crossover study, 12 healthy volunteers took 600 mg rifampicin or placebo once daily for 5 days (Tapaninen et al 2010). On the morning of day 6, a venous blood RNA sample was collected from each participant into a PaxGene® tube. The expression of 18 ABC, 24 SLC and 10 SLCO transporters was investigated using reverse transcription quantitative real-time PCR (RT-qPCR) with OpenArray® technology on a QuantStudio™ 12 K Flex Real-Time PCR system (Life Technologies, Paisley, UK). FPGS, TRAP1, DECR1 and PPIB served as reference genes. A total of 16 ABC transporters, 18 SLC transporters and 4 SLCO transporters were expressed above the quantification limit in most samples. Rifampicin had no significant effect on the expression of any transporter. However, SLC5A6 (sodium-dependent multivitamin transporter, SMVT) and ABCB4 (multidrug resistance protein 3, MDR3) expression tended to be increased by rifampicin (by 19% and 18%; P=0.066 and P=0.096, respectively). In conclusion, multiple drug transporter genes are expressed in whole blood, but rifampicin has limited effects on their expression. References: Tapaninen T, Neuvonen PJ, Niemi M. Rifampicin reduces the plasma concentrations and the renin-inhibiting effect of aliskiren. Eur J Clin Pharmacol 2010;66:497-502.
Subject: rifampicin
pharmacology
pharmacogenomics
drug transporters
PXR


Files in this item

Files Size Format View

There are no files associated with this item.

This item appears in the following Collection(s)

Show full item record