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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Journal of Personalized Medicine |
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| Online Access: | https://www.mdpi.com/2075-4426/13/3/489 |
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| author | Miriam Saiz-Rodríguez Dolores Ochoa Pablo Zubiaur Marcos Navares-Gómez Manuel Román Paola Camargo-Mamani Sergio Luquero-Bueno Gonzalo Villapalos-García Raquel Alcaraz Gina Mejía-Abril Estefanía Santos-Mazo Francisco Abad-Santos |
| author_facet | Miriam Saiz-Rodríguez Dolores Ochoa Pablo Zubiaur Marcos Navares-Gómez Manuel Román Paola Camargo-Mamani Sergio Luquero-Bueno Gonzalo Villapalos-García Raquel Alcaraz Gina Mejía-Abril Estefanía Santos-Mazo Francisco Abad-Santos |
| author_sort | Miriam Saiz-Rodríguez |
| collection | DOAJ |
| 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 <i>SLC22A4</i> and <i>SLC47A2</i> 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 <i>SLC22A3</i> and <i>SLC22A4</i>, influenced AUC. The maximum concentration was affected by age and <i>SLC22A1</i>, but after adjusting for dW, it was affected by sex, age, ethnicity, <i>ABCG2</i>, and <i>SLC22A4</i>. The time to reach the maximum concentration was influenced by sex, like half-life, which was also affected by <i>SLC22A3</i>. The volume of distribution and clearance was affected by sex, age, ethnicity and <i>SLC22A3</i>. Alternatively, the pharmacokinetics of metformin was unaffected by polymorphisms in <i>ABCB1</i>, <i>SLC2A2</i>, <i>SLC22A2</i>, or <i>SLC47A1</i>. Therefore, our study demonstrates that a multifactorial approach to all patient characteristics is necessary for better individualization. |
| first_indexed | 2024-03-11T06:19:23Z |
| format | Article |
| id | doaj.art-9d25e1ecface4e53bf561d00f3056b59 |
| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-11T06:19:23Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-9d25e1ecface4e53bf561d00f3056b592023-11-17T12:03:04ZengMDPI AGJournal of Personalized Medicine2075-44262023-03-0113348910.3390/jpm13030489Identification of Transporter Polymorphisms Influencing Metformin Pharmacokinetics in Healthy VolunteersMiriam Saiz-Rodríguez0Dolores Ochoa1Pablo Zubiaur2Marcos Navares-Gómez3Manuel Román4Paola Camargo-Mamani5Sergio Luquero-Bueno6Gonzalo Villapalos-García7Raquel Alcaraz8Gina Mejía-Abril9Estefanía Santos-Mazo10Francisco Abad-Santos11Research Unit, Fundación Burgos por la Investigación de la Salud (FBIS), Hospital Universitario de Burgos, 09006 Burgos, SpainClinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Teófilo Hernando, Instituto de Investigación Sanitaria La Princesa (IP), Universidad Autónoma de Madrid (UAM), 28006 Madrid, SpainClinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Teófilo Hernando, Instituto de Investigación Sanitaria La Princesa (IP), Universidad Autónoma de Madrid (UAM), 28006 Madrid, SpainClinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Teófilo Hernando, Instituto de Investigación Sanitaria La Princesa (IP), Universidad Autónoma de Madrid (UAM), 28006 Madrid, SpainClinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Teófilo Hernando, Instituto de Investigación Sanitaria La Princesa (IP), Universidad Autónoma de Madrid (UAM), 28006 Madrid, SpainClinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Teófilo Hernando, Instituto de Investigación Sanitaria La Princesa (IP), Universidad Autónoma de Madrid (UAM), 28006 Madrid, SpainClinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Teófilo Hernando, Instituto de Investigación Sanitaria La Princesa (IP), Universidad Autónoma de Madrid (UAM), 28006 Madrid, SpainClinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Teófilo Hernando, Instituto de Investigación Sanitaria La Princesa (IP), Universidad Autónoma de Madrid (UAM), 28006 Madrid, SpainResearch Unit, Fundación Burgos por la Investigación de la Salud (FBIS), Hospital Universitario de Burgos, 09006 Burgos, SpainClinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Teófilo Hernando, Instituto de Investigación Sanitaria La Princesa (IP), Universidad Autónoma de Madrid (UAM), 28006 Madrid, SpainEndocrinology Department, Hospital Universitario de Burgos, 09006 Burgos, SpainClinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Teófilo Hernando, Instituto de Investigación Sanitaria La Princesa (IP), Universidad Autónoma de Madrid (UAM), 28006 Madrid, SpainFor 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 <i>SLC22A4</i> and <i>SLC47A2</i> 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 <i>SLC22A3</i> and <i>SLC22A4</i>, influenced AUC. The maximum concentration was affected by age and <i>SLC22A1</i>, but after adjusting for dW, it was affected by sex, age, ethnicity, <i>ABCG2</i>, and <i>SLC22A4</i>. The time to reach the maximum concentration was influenced by sex, like half-life, which was also affected by <i>SLC22A3</i>. The volume of distribution and clearance was affected by sex, age, ethnicity and <i>SLC22A3</i>. Alternatively, the pharmacokinetics of metformin was unaffected by polymorphisms in <i>ABCB1</i>, <i>SLC2A2</i>, <i>SLC22A2</i>, or <i>SLC47A1</i>. Therefore, our study demonstrates that a multifactorial approach to all patient characteristics is necessary for better individualization.https://www.mdpi.com/2075-4426/13/3/489metforminpharmacogeneticstransportersSLCABCsex |
| spellingShingle | Miriam Saiz-Rodríguez Dolores Ochoa Pablo Zubiaur Marcos Navares-Gómez Manuel Román Paola Camargo-Mamani Sergio Luquero-Bueno Gonzalo Villapalos-García Raquel Alcaraz Gina Mejía-Abril Estefanía Santos-Mazo Francisco Abad-Santos Identification of Transporter Polymorphisms Influencing Metformin Pharmacokinetics in Healthy Volunteers Journal of Personalized Medicine metformin pharmacogenetics transporters SLC ABC sex |
| title | 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_short | Identification of Transporter Polymorphisms Influencing Metformin Pharmacokinetics in Healthy Volunteers |
| title_sort | identification of transporter polymorphisms influencing metformin pharmacokinetics in healthy volunteers |
| topic | metformin pharmacogenetics transporters SLC ABC sex |
| url | https://www.mdpi.com/2075-4426/13/3/489 |
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