Identification of transporter polymorphisms influencing metformin pharmacokinetics in healthy volunteers
For patients with type 2 diabetes, metformin is the most often recommended drug. However, there are substantial individual differences in the pharmacological response to metformin. To investigate the effect of transporter polymorphisms on metformin pharmacokinetics in an environment free of confound...
| Autores: | , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2023 |
| País: | España |
| Institución: | Universidad Autónoma de Madrid |
| Repositorio: | Biblos-e Archivo. Repositorio Institucional de la UAM |
| Idioma: | inglés |
| OAI Identifier: | oai:repositorio.uam.es:10486/708739 |
| Acceso en línea: | http://hdl.handle.net/10486/708739 https://dx.doi.org/10.3390/jpm13030489 |
| Access Level: | acceso abierto |
| Palabra clave: | metformin pharmacogenetics transporters SLC ABC sex ethnicity Medicina |
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Identification of transporter polymorphisms influencing metformin pharmacokinetics in healthy volunteersSaiz Rodríguez, MiriamOchoa Mazarro, María DoloresZubiaur Precioso, PabloNavares-Gómez, MarcosRomán, ManuelCamargo-Mamani, PaolaLuquero-Bueno, SergioVillapalos-García, GonzaloAlcaraz, RaquelMejía Abril, GinaSantos-Mazo, EstefaníaAbad Santos, FranciscometforminpharmacogeneticstransportersSLCABCsexethnicityMedicinaFor patients with type 2 diabetes, metformin is the most often recommended drug. However, there are substantial individual differences in the pharmacological response to metformin. To investigate the effect of transporter polymorphisms on metformin pharmacokinetics in an environment free of confounding variables, we conducted our study on healthy participants. This is the first investigation to consider demographic characteristics alongside all transporters involved in metformin distribution. Pharmacokinetic parameters of metformin were found to be affected by age, sex, ethnicity, and several polymorphisms. Age and SLC22A4 and SLC47A2 polymorphisms affected the area under the concentration-time curve (AUC). However, after adjusting for dose-to-weight ratio (dW), sex, age, and ethnicity, along with SLC22A3 and SLC22A4, influenced AUC. The maximum concentration was affected by age and SLC22A1, but after adjusting for dW, it was affected by sex, age, ethnicity, ABCG2, and SLC22A4. The time to reach the maximum concentration was influenced by sex, like half-life, which was also affected by SLC22A3. The volume of distribution and clearance was affected by sex, age, ethnicity and SLC22A3. Alternatively, the pharmacokinetics of metformin was unaffected by polymorphisms in ABCB1, SLC2A2, SLC22A2, or SLC47A1. Therefore, our study demonstrates that a multifactorial approach to all patient characteristics is necessary for better individualizationThe project was financed by the Regional Health Management of Castilla y León (GRS 2432/A/21) and partially by Fundación Burgos por la Investigación de la Salud (FBIS). M.S.R. research is supported by Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Science and Innovation, through the Sara Borrell Program (CD21/00022). G.V.G. is cofinanced by Instituto de Salud Carlos III (ISCIII) and the European Social Fund (PFIS predoctoral grant, number FI20/00090). M.N.G. is financed by the ICI20/00131 grant, Acción Estratégica en Salud 2017–2020, ISCIII. P.Z. is financed by Universidad Autónoma de Madrid, Margarita Salas contract, grants for the requalification of the Spanish university system. The MassArray genotyping service was carried out at the Spanish genotyping center–Centro Español de Genotipado CEGEN-PRB3-ISCIII, which is supported by grant PT17/0019 of the PE I+D+i 2013–2016, funded by ISCIII and European Regional Development Fund ERDFMDPIDepartamento de FarmacologíaFacultad de Medicina20232023-03-08research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/708739https://dx.doi.org/10.3390/jpm13030489reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7087392026-06-23T12:46:27Z |
| dc.title.none.fl_str_mv |
Identification of transporter polymorphisms influencing metformin pharmacokinetics in healthy volunteers |
| title |
Identification of transporter polymorphisms influencing metformin pharmacokinetics in healthy volunteers |
| spellingShingle |
Identification of transporter polymorphisms influencing metformin pharmacokinetics in healthy volunteers Saiz Rodríguez, Miriam metformin pharmacogenetics transporters SLC ABC sex ethnicity Medicina |
| title_short |
Identification of transporter polymorphisms influencing metformin pharmacokinetics in healthy volunteers |
| title_full |
Identification of transporter polymorphisms influencing metformin pharmacokinetics in healthy volunteers |
| title_fullStr |
Identification of transporter polymorphisms influencing metformin pharmacokinetics in healthy volunteers |
| title_full_unstemmed |
Identification of transporter polymorphisms influencing metformin pharmacokinetics in healthy volunteers |
| title_sort |
Identification of transporter polymorphisms influencing metformin pharmacokinetics in healthy volunteers |
| dc.creator.none.fl_str_mv |
Saiz Rodríguez, Miriam Ochoa Mazarro, María Dolores Zubiaur Precioso, Pablo Navares-Gómez, Marcos Román, Manuel Camargo-Mamani, Paola Luquero-Bueno, Sergio Villapalos-García, Gonzalo Alcaraz, Raquel Mejía Abril, Gina Santos-Mazo, Estefanía Abad Santos, Francisco |
| author |
Saiz Rodríguez, Miriam |
| author_facet |
Saiz Rodríguez, Miriam Ochoa Mazarro, María Dolores Zubiaur Precioso, Pablo Navares-Gómez, Marcos Román, Manuel Camargo-Mamani, Paola Luquero-Bueno, Sergio Villapalos-García, Gonzalo Alcaraz, Raquel Mejía Abril, Gina Santos-Mazo, Estefanía Abad Santos, Francisco |
| author_role |
author |
| author2 |
Ochoa Mazarro, María Dolores Zubiaur Precioso, Pablo Navares-Gómez, Marcos Román, Manuel Camargo-Mamani, Paola Luquero-Bueno, Sergio Villapalos-García, Gonzalo Alcaraz, Raquel Mejía Abril, Gina Santos-Mazo, Estefanía Abad Santos, Francisco |
| author2_role |
author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Departamento de Farmacología Facultad de Medicina |
| dc.subject.none.fl_str_mv |
metformin pharmacogenetics transporters SLC ABC sex ethnicity Medicina |
| topic |
metformin pharmacogenetics transporters SLC ABC sex ethnicity Medicina |
| description |
For patients with type 2 diabetes, metformin is the most often recommended drug. However, there are substantial individual differences in the pharmacological response to metformin. To investigate the effect of transporter polymorphisms on metformin pharmacokinetics in an environment free of confounding variables, we conducted our study on healthy participants. This is the first investigation to consider demographic characteristics alongside all transporters involved in metformin distribution. Pharmacokinetic parameters of metformin were found to be affected by age, sex, ethnicity, and several polymorphisms. Age and SLC22A4 and SLC47A2 polymorphisms affected the area under the concentration-time curve (AUC). However, after adjusting for dose-to-weight ratio (dW), sex, age, and ethnicity, along with SLC22A3 and SLC22A4, influenced AUC. The maximum concentration was affected by age and SLC22A1, but after adjusting for dW, it was affected by sex, age, ethnicity, ABCG2, and SLC22A4. The time to reach the maximum concentration was influenced by sex, like half-life, which was also affected by SLC22A3. The volume of distribution and clearance was affected by sex, age, ethnicity and SLC22A3. Alternatively, the pharmacokinetics of metformin was unaffected by polymorphisms in ABCB1, SLC2A2, SLC22A2, or SLC47A1. Therefore, our study demonstrates that a multifactorial approach to all patient characteristics is necessary for better individualization |
| publishDate |
2023 |
| dc.date.none.fl_str_mv |
2023 2023-03-08 |
| dc.type.none.fl_str_mv |
research article http://purl.org/coar/resource_type/c_2df8fbb1 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
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article |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10486/708739 https://dx.doi.org/10.3390/jpm13030489 |
| url |
http://hdl.handle.net/10486/708739 https://dx.doi.org/10.3390/jpm13030489 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 |
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openAccess |
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application/pdf |
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MDPI |
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MDPI |
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reponame:Biblos-e Archivo. Repositorio Institucional de la UAM instname:Universidad Autónoma de Madrid |
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Universidad Autónoma de Madrid |
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