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

Show simple item record 2016-06-15T10:25:59Z 2016-06-15T10:25:59Z
dc.title Impact of the PXR-activator rifampicin on drug transporter gene expression in whole blood en
ethesis.discipline Clinical Pharmacology and Pharmacotherapy en
ethesis.discipline Kliininen farmakologia ja lääkehoito fi
ethesis.discipline Klinisk farmakologi och läkemedelsbehandling sv
ethesis.faculty Medicinska fakulteten sv
ethesis.faculty Lääketieteellinen tiedekunta fi
ethesis.faculty Faculty of Medicine en
ethesis.faculty.URI Helsingfors universitet sv University of Helsinki en Helsingin yliopisto fi
dct.creator Peled, Nitai
dct.issued 2014
dct.language.ISO639-2 eng
dct.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. en
dct.subject rifampicin en
dct.subject pharmacology en
dct.subject pharmacogenomics en
dct.subject drug transporters en
dct.subject PXR
dct.language en
ethesis.language English en
ethesis.language englanti fi
ethesis.language engelska sv
ethesis.supervisor Niemi, Mikko
ethesis.thesistype pro gradu-avhandlingar sv
ethesis.thesistype pro gradu -tutkielmat fi
ethesis.thesistype master's thesis en
dct.identifier.ethesis E-thesisID:1b3694ea-3394-4f26-be71-648f88558c70
ethesis.degreeprogram Translationaalisen lääketieteen maisteriohjelma fi
ethesis.degreeprogram Master's Degree Programme in Translational Medicine en
ethesis.degreeprogram Magisterprogram i translationell medicin sv
ethesis-internal.timestamp.reviewStep 2016-06-07 08:29:25:366
dct.identifier.urn URN:NBN:fi:hulib-201606152425
dc.type.dcmitype Text

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