A nonsynonymous variation in MRP2/ABCC2 is associated with neurological adverse drug reactions of carbamazepine in patients with epilepsy

Kim, Won Joo; Lee, Ji Hyun; Yi, Jihyun; Cho, Yang-Je; Heo, Kyoung; Lee, Sung Hee; Kim, So Won; Kim, Myeong-Kyu; Kim, Kyung Hwan; Lee, Ki Young; Lee, Min Goo

doi:10.1097/fpc.0b013e328338073a

Cited by 102 publications

(63 citation statements)

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“…It is noteworthy that the SNP 21214GϾA (V417I; rs2273697; 16 heterozygotes, 2 homozygotes), which has not been reported to affect MRP2 expression, showed a significantly (P Ͻ 0.004) higher expression of MRP2 (1.87 Ϯ 0.77 fmol/g membrane protein; n ϭ 18) versus the wild-type livers (1.34 Ϯ 0.38 fmol/g membrane protein; n ϭ 27). This SNP has been associated with greater central nervous system adverse effects (but not efficacy) of carbamazepine, presumably because of lower MRP2 activity (Kim et al, 2010). It is possible that this SNP increases the expression of MRP2 while reducing its activity.…”

Section: Resultsmentioning

confidence: 99%

Interindividual Variability in Hepatic Expression of the Multidrug Resistance-Associated Protein 2 (MRP2/ABCC2): Quantification by Liquid Chromatography/Tandem Mass Spectrometry

Deo¹,

Prasad²,

Balogh³

et al. 2012

Drug Metab Dispos

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ABSTRACT:Multidrug-associated protein 2 (MRP2) is an efflux transporter that is expressed at the bile canalicular membrane. To allow in vitro to in vivo extrapolation of the contribution of MRP2 toward hepatic disposition of its substrates, data on the interindividual variability of hepatic MRP2 protein expression are required. Therefore, we quantified the expression of MRP2 in the University of Washington (UW) human liver bank (n ‫؍‬ 51) using a modified version of a previously validated liquid chromatography/ tandem mass spectrometry assay. An unlabeled (LTIIPQDPILFSGSLR) and stable isotope-labeled (LTIIPQDPILFSGSL[ Quality control samples created by spiking human serum albumin or pooled human liver (n ‫؍‬ 51) matrix with three different MRP2 synthetic peptide concentrations generated error and precision values of less than 15%. As determined by the surrogate peptide, the average MRP2 expression in the UW liver bank samples was 1.54 ؎ 0.64 fmol/g liver membrane protein and was found to be independent of age (7-63 years) or sex. A single nucleotide polymorphism in the promoter region (rs717620), previously thought to affect MRP2 expression, did not influence hepatic expression of MRP2. In contrast, the single nucleotide polymorphism 21214G>A (V417I; rs2273697) was associated with significantly higher hepatic MRP2 expression.

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Section: Resultsmentioning

confidence: 99%

Interindividual Variability in Hepatic Expression of the Multidrug Resistance-Associated Protein 2 (MRP2/ABCC2): Quantification by Liquid Chromatography/Tandem Mass Spectrometry

Deo¹,

Prasad²,

Balogh³

et al. 2012

Drug Metab Dispos

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“…In vitro and in vivo studies have suggested that CBZ or its active metabolite is a substrate of ABCC2 and can interfere with drug efficacy by effluxing it out (6,16). ABCC2 has been demonstrated to be involved in CBZ efficacy in the ABCC2-deficient rat model (6).…”

Section: Introductionmentioning

confidence: 98%

Exploring the Carbamazepine Interaction with Human Pregnane X Receptor and Effect on ABCC2 Using in Vitro and in Silico Approach

et al. 2017

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“…Genotypes of OATP1B1 are associated with interindividual differences in the systemic exposure of statins (Nishizato et al, 2003;Chung et al, 2005;Lee et al, 2005;Pasanen et al, 2006Pasanen et al, , 2007. Another report has described the association of single nucleotide polymorphisms of MRP2 with the plasma levels of its substrates, phase II metabolites of isoflavonoids (Kato et al, 2012), or adverse reactions to drugs (Kim et al, 2010). [ 11 C]DPV will provide quantitative information on the effect of single nucleotide polymorphisms on OATP1B1 and MRP2 activities.…”

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confidence: 99%

Evaluation of Oatp and Mrp2 Activities in Hepatobiliary Excretion Using Newly Developed Positron Emission Tomography Tracer [¹¹C]Dehydropravastatin in Rats

Shingaki

Takashima²,

Ijuin³

et al. 2013

J Pharmacol Exp Ther

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We developed a pravastatin derivative, sodium (3R,5R)-3,5-dihydroxy-7-((1S,2S,6S,8S)-6-hydroxy-2-methyl-8-((1-[ 11 C]-(E)-2-methyl-but-2-enoyl)oxy)-1,2,6,7,8,8a-hexahydronaphthalen-1-yl)heptanoate ([ 11 C]DPV), as a positron emission tomography (PET) probe for noninvasive measurement of hepatobiliary transport, and conducted pharmacokinetic analysis in rats as a feasibility study for future clinical study. Transport activities of DPV in freshly isolated rat hepatocytes and rodent multidrug resistance-associated protein 2 (rMrp2; human, MRP2)-expressing membrane vesicles were similar to those of pravastatin. Rifampicin diminished the uptake of DPV and pravastatin by the hepatocytes, with similar inhibition potency. [11 C]DPV underwent biotransformation to produce at least two metabolites in rat, but metabolism of [ 11 C]DPV occurred negligibly in human hepatocytes during a 90-minute incubation. After intravenous injection, [11 C]DPV was mainly distributed to the liver and kidneys, where the tissue uptake clearances (CL uptake,liver and CL uptake,kidney ) were blood-flow-limited (73.6 6 4.8 and 24.6 6 0.6 ml/min per kilogram, respectively). Systemic elimination of [ 11 C]DPV was delayed in rifampicin-treated rat and an Mrp2-deficient mutant rat, Eisai hyperbilirubinemic mutant rat (EHBR). Rifampicin treatment decreased both CL uptake,liver and CL uptake,kidney of [ 11 C]DPV by 30% (P , 0.05), whereas these parameters were unchanged in EHBR. Meanwhile, the canalicular efflux clearance (CL int,bile ) of [ 11 C]DPV, which was 12.2 6 1.5 ml/min per kilogram in the control rat, decreased by 60% and 89% in rifampicin-treated rat and EHBR (P , 0.05), respectively. These results indicate that [

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A nonsynonymous variation in MRP2/ABCC2 is associated with neurological adverse drug reactions of carbamazepine in patients with epilepsy

Abstract: These results strongly suggest that the A-allele of the MRP2 single nucleotide polymorphism c.1247G>A is associated with adverse neurological drug reactions to carbamazepine.

Cited by 102 publications

References 36 publications

Interindividual Variability in Hepatic Expression of the Multidrug Resistance-Associated Protein 2 (MRP2/ABCC2): Quantification by Liquid Chromatography/Tandem Mass Spectrometry

Interindividual Variability in Hepatic Expression of the Multidrug Resistance-Associated Protein 2 (MRP2/ABCC2): Quantification by Liquid Chromatography/Tandem Mass Spectrometry

Exploring the Carbamazepine Interaction with Human Pregnane X Receptor and Effect on ABCC2 Using in Vitro and in Silico Approach

Evaluation of Oatp and Mrp2 Activities in Hepatobiliary Excretion Using Newly Developed Positron Emission Tomography Tracer [¹¹C]Dehydropravastatin in Rats

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A nonsynonymous variation in MRP2/ABCC2 is associated with neurological adverse drug reactions of carbamazepine in patients with epilepsy

Abstract: These results strongly suggest that the A-allele of the MRP2 single nucleotide polymorphism c.1247G>A is associated with adverse neurological drug reactions to carbamazepine.

Cited by 102 publications

References 36 publications

Interindividual Variability in Hepatic Expression of the Multidrug Resistance-Associated Protein 2 (MRP2/ABCC2): Quantification by Liquid Chromatography/Tandem Mass Spectrometry

Interindividual Variability in Hepatic Expression of the Multidrug Resistance-Associated Protein 2 (MRP2/ABCC2): Quantification by Liquid Chromatography/Tandem Mass Spectrometry

Exploring the Carbamazepine Interaction with Human Pregnane X Receptor and Effect on ABCC2 Using in Vitro and in Silico Approach

Evaluation of Oatp and Mrp2 Activities in Hepatobiliary Excretion Using Newly Developed Positron Emission Tomography Tracer [11C]Dehydropravastatin in Rats

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Evaluation of Oatp and Mrp2 Activities in Hepatobiliary Excretion Using Newly Developed Positron Emission Tomography Tracer [¹¹C]Dehydropravastatin in Rats