Impact of the superoxide dismutase 2 Val16Ala polymorphism on the relationship between valproic acid exposure and elevation of γ-glutamyltransferase in patients with epilepsy: a population pharmacokinetic-pharmacodynamic analysis.

<h4>Background</h4>There has been accumulating evidence that there are associations among γ-glutamyltransferase (γ-GT) elevation and all-cause mortality, cardiovascular diseases and metabolic diseases, including nonalcoholic fatty liver disease. The primary objective of this study was to...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Naoki Ogusu, Junji Saruwatari, Hiroo Nakashima, Madoka Noai, Miki Nishimura, Mariko Deguchi, Kentaro Oniki, Norio Yasui-Furukori, Sunao Kaneko, Takateru Ishitsu, Kazuko Nakagaswa
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/56f37d4bfa8b4f728fc3181cce8130ad
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:56f37d4bfa8b4f728fc3181cce8130ad
record_format	dspace
spelling	oai:doaj.org-article:56f37d4bfa8b4f728fc3181cce8130ad2021-11-25T05:54:37ZImpact of the superoxide dismutase 2 Val16Ala polymorphism on the relationship between valproic acid exposure and elevation of γ-glutamyltransferase in patients with epilepsy: a population pharmacokinetic-pharmacodynamic analysis.1932-620310.1371/journal.pone.0111066https://doaj.org/article/56f37d4bfa8b4f728fc3181cce8130ad2014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0111066https://doaj.org/toc/1932-6203<h4>Background</h4>There has been accumulating evidence that there are associations among γ-glutamyltransferase (γ-GT) elevation and all-cause mortality, cardiovascular diseases and metabolic diseases, including nonalcoholic fatty liver disease. The primary objective of this study was to evaluate the impact of the most common and potentially functional polymorphisms of antioxidant enzyme genes, i.e. superoxide dismutase 2 (SOD2), glutathione S-transferase M1 and glutathione S-transferase T1, on the γ-GT elevation during valproic acid (VPA) therapy.<h4>Methods and findings</h4>This retrospective study included 237 and 169 VPA-treated Japanese patients with epilepsy for population pharmacokinetic and pharmacokinetic-pharmacodynamic analyses, respectively. A nonlinear mixed-effect model represented the pharmacokinetics of VPA and the relationships between VPA exposure and γ-GT elevation. A one-compartment model of the pharmacokinetic parameters of VPA adequately described the data; while the model for the probability of the γ-GT elevation was fitted using a logistic regression model, in which the logit function of the probability was a linear function of VPA exposure. The SOD2 Val16Ala polymorphism and complication with intellectual disability were found to be significant covariates influencing the intercept of the logit function for the probability of an elevated γ-GT level. The predicted mean percentages of the subjects with γ-GT elevation were about 2- to 3-fold, 3- to 4-fold and 4- to 8-fold greater in patients with the SOD2 Val/Val genotype but without any intellectual disability, those with the SOD2 Val/Ala or Ala/Ala genotype and intellectual disability and those with the SOD2 Val/Val genotype and intellectual disability, respectively, compared to those with the SOD2 Val/Ala or Ala/Ala genotype without intellectual disability.<h4>Conclusion</h4>Our results showed that the SOD2 Val16Ala polymorphism has an impact on the relationship between VPA exposure and γ-GT elevation in patients with epilepsy. These results suggest that determining the SOD2 genotype could be helpful for preventing the VPA-induced γ-GT elevation.Naoki OgusuJunji SaruwatariHiroo NakashimaMadoka NoaiMiki NishimuraMariko DeguchiKentaro OnikiNorio Yasui-FurukoriSunao KanekoTakateru IshitsuKazuko NakagaswaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 11, p e111066 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Naoki Ogusu Junji Saruwatari Hiroo Nakashima Madoka Noai Miki Nishimura Mariko Deguchi Kentaro Oniki Norio Yasui-Furukori Sunao Kaneko Takateru Ishitsu Kazuko Nakagaswa Impact of the superoxide dismutase 2 Val16Ala polymorphism on the relationship between valproic acid exposure and elevation of γ-glutamyltransferase in patients with epilepsy: a population pharmacokinetic-pharmacodynamic analysis.
description	<h4>Background</h4>There has been accumulating evidence that there are associations among γ-glutamyltransferase (γ-GT) elevation and all-cause mortality, cardiovascular diseases and metabolic diseases, including nonalcoholic fatty liver disease. The primary objective of this study was to evaluate the impact of the most common and potentially functional polymorphisms of antioxidant enzyme genes, i.e. superoxide dismutase 2 (SOD2), glutathione S-transferase M1 and glutathione S-transferase T1, on the γ-GT elevation during valproic acid (VPA) therapy.<h4>Methods and findings</h4>This retrospective study included 237 and 169 VPA-treated Japanese patients with epilepsy for population pharmacokinetic and pharmacokinetic-pharmacodynamic analyses, respectively. A nonlinear mixed-effect model represented the pharmacokinetics of VPA and the relationships between VPA exposure and γ-GT elevation. A one-compartment model of the pharmacokinetic parameters of VPA adequately described the data; while the model for the probability of the γ-GT elevation was fitted using a logistic regression model, in which the logit function of the probability was a linear function of VPA exposure. The SOD2 Val16Ala polymorphism and complication with intellectual disability were found to be significant covariates influencing the intercept of the logit function for the probability of an elevated γ-GT level. The predicted mean percentages of the subjects with γ-GT elevation were about 2- to 3-fold, 3- to 4-fold and 4- to 8-fold greater in patients with the SOD2 Val/Val genotype but without any intellectual disability, those with the SOD2 Val/Ala or Ala/Ala genotype and intellectual disability and those with the SOD2 Val/Val genotype and intellectual disability, respectively, compared to those with the SOD2 Val/Ala or Ala/Ala genotype without intellectual disability.<h4>Conclusion</h4>Our results showed that the SOD2 Val16Ala polymorphism has an impact on the relationship between VPA exposure and γ-GT elevation in patients with epilepsy. These results suggest that determining the SOD2 genotype could be helpful for preventing the VPA-induced γ-GT elevation.
format	article
author	Naoki Ogusu Junji Saruwatari Hiroo Nakashima Madoka Noai Miki Nishimura Mariko Deguchi Kentaro Oniki Norio Yasui-Furukori Sunao Kaneko Takateru Ishitsu Kazuko Nakagaswa
author_facet	Naoki Ogusu Junji Saruwatari Hiroo Nakashima Madoka Noai Miki Nishimura Mariko Deguchi Kentaro Oniki Norio Yasui-Furukori Sunao Kaneko Takateru Ishitsu Kazuko Nakagaswa
author_sort	Naoki Ogusu
title	Impact of the superoxide dismutase 2 Val16Ala polymorphism on the relationship between valproic acid exposure and elevation of γ-glutamyltransferase in patients with epilepsy: a population pharmacokinetic-pharmacodynamic analysis.
title_short	Impact of the superoxide dismutase 2 Val16Ala polymorphism on the relationship between valproic acid exposure and elevation of γ-glutamyltransferase in patients with epilepsy: a population pharmacokinetic-pharmacodynamic analysis.
title_full	Impact of the superoxide dismutase 2 Val16Ala polymorphism on the relationship between valproic acid exposure and elevation of γ-glutamyltransferase in patients with epilepsy: a population pharmacokinetic-pharmacodynamic analysis.
title_fullStr	Impact of the superoxide dismutase 2 Val16Ala polymorphism on the relationship between valproic acid exposure and elevation of γ-glutamyltransferase in patients with epilepsy: a population pharmacokinetic-pharmacodynamic analysis.
title_full_unstemmed	Impact of the superoxide dismutase 2 Val16Ala polymorphism on the relationship between valproic acid exposure and elevation of γ-glutamyltransferase in patients with epilepsy: a population pharmacokinetic-pharmacodynamic analysis.
title_sort	impact of the superoxide dismutase 2 val16ala polymorphism on the relationship between valproic acid exposure and elevation of γ-glutamyltransferase in patients with epilepsy: a population pharmacokinetic-pharmacodynamic analysis.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/56f37d4bfa8b4f728fc3181cce8130ad
work_keys_str_mv	AT naokiogusu impactofthesuperoxidedismutase2val16alapolymorphismontherelationshipbetweenvalproicacidexposureandelevationofgglutamyltransferaseinpatientswithepilepsyapopulationpharmacokineticpharmacodynamicanalysis AT junjisaruwatari impactofthesuperoxidedismutase2val16alapolymorphismontherelationshipbetweenvalproicacidexposureandelevationofgglutamyltransferaseinpatientswithepilepsyapopulationpharmacokineticpharmacodynamicanalysis AT hiroonakashima impactofthesuperoxidedismutase2val16alapolymorphismontherelationshipbetweenvalproicacidexposureandelevationofgglutamyltransferaseinpatientswithepilepsyapopulationpharmacokineticpharmacodynamicanalysis AT madokanoai impactofthesuperoxidedismutase2val16alapolymorphismontherelationshipbetweenvalproicacidexposureandelevationofgglutamyltransferaseinpatientswithepilepsyapopulationpharmacokineticpharmacodynamicanalysis AT mikinishimura impactofthesuperoxidedismutase2val16alapolymorphismontherelationshipbetweenvalproicacidexposureandelevationofgglutamyltransferaseinpatientswithepilepsyapopulationpharmacokineticpharmacodynamicanalysis AT marikodeguchi impactofthesuperoxidedismutase2val16alapolymorphismontherelationshipbetweenvalproicacidexposureandelevationofgglutamyltransferaseinpatientswithepilepsyapopulationpharmacokineticpharmacodynamicanalysis AT kentarooniki impactofthesuperoxidedismutase2val16alapolymorphismontherelationshipbetweenvalproicacidexposureandelevationofgglutamyltransferaseinpatientswithepilepsyapopulationpharmacokineticpharmacodynamicanalysis AT norioyasuifurukori impactofthesuperoxidedismutase2val16alapolymorphismontherelationshipbetweenvalproicacidexposureandelevationofgglutamyltransferaseinpatientswithepilepsyapopulationpharmacokineticpharmacodynamicanalysis AT sunaokaneko impactofthesuperoxidedismutase2val16alapolymorphismontherelationshipbetweenvalproicacidexposureandelevationofgglutamyltransferaseinpatientswithepilepsyapopulationpharmacokineticpharmacodynamicanalysis AT takateruishitsu impactofthesuperoxidedismutase2val16alapolymorphismontherelationshipbetweenvalproicacidexposureandelevationofgglutamyltransferaseinpatientswithepilepsyapopulationpharmacokineticpharmacodynamicanalysis AT kazukonakagaswa impactofthesuperoxidedismutase2val16alapolymorphismontherelationshipbetweenvalproicacidexposureandelevationofgglutamyltransferaseinpatientswithepilepsyapopulationpharmacokineticpharmacodynamicanalysis
_version_	1718414400841318400

Impact of the superoxide dismutase 2 Val16Ala polymorphism on the relationship between valproic acid exposure and elevation of γ-glutamyltransferase in patients with epilepsy: a population pharmacokinetic-pharmacodynamic analysis.

Ejemplares similares