Pharmacogenetics of Donepezil and Memantine in Healthy Subjects
Donepezil and memantine are the most common drugs used for Alzheimer’s disease. Their low effectiveness could partly be explained by genetic factors. Thus, we aim to identify Single Nucleotide Polymorphisms (SNPs) associated with pharmacokinetics, pharmacodynamics, and the safety of donepezil and me...
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| Format: | Article |
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MDPI AG
2022-05-01
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| Series: | Journal of Personalized Medicine |
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| Online Access: | https://www.mdpi.com/2075-4426/12/5/788 |
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| author | María C. Ovejero-Benito Dolores Ochoa Teresa Enrique-Benedito Miriam del Peso-Casado Pablo Zubiaur Marcos Navares Manuel Román Francisco Abad-Santos |
| author_facet | María C. Ovejero-Benito Dolores Ochoa Teresa Enrique-Benedito Miriam del Peso-Casado Pablo Zubiaur Marcos Navares Manuel Román Francisco Abad-Santos |
| author_sort | María C. Ovejero-Benito |
| collection | DOAJ |
| description | Donepezil and memantine are the most common drugs used for Alzheimer’s disease. Their low effectiveness could partly be explained by genetic factors. Thus, we aim to identify Single Nucleotide Polymorphisms (SNPs) associated with pharmacokinetics, pharmacodynamics, and the safety of donepezil and memantine. For this regard, 25 volunteers enrolled in a bioequivalence clinical trial were genotyped for 67 SNPs in 21 genes with a ThermoFisher QuantStudio 12K Flex OpenArray. The statistical strategy included a univariate analysis that analyzed the association of these SNPs with pharmacokinetic parameters or the development of adverse drug reactions (ADRs) followed by a Bonferroni-corrected multivariate regression. Statistical analyses were performed with SPSS software v.21 and R commander (version v3.6.3). In the univariate analysis, fourteen and sixteen SNPs showed a significant association with memantine’s and donepezil’s pharmacokinetic parameters, respectively. Rs20417 (<i>PTGS2</i>) was associated with the development of at least one ADR. However, none of these associations reached the significance threshold in the Bonferroni-corrected multivariate analysis. In conclusion, we did not observe any significant association of the SNPs analyzed with memantine and donepezil pharmacokinetics or ADRs. Current evidence on memantine and donepezil pharmacogenetics does not justify their inclusion in pharmacogenetic guidelines. |
| first_indexed | 2024-03-10T03:35:21Z |
| format | Article |
| id | doaj.art-0943156cb47242268098ab3143fa3ebd |
| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-10T03:35:21Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-0943156cb47242268098ab3143fa3ebd2023-11-23T11:44:44ZengMDPI AGJournal of Personalized Medicine2075-44262022-05-0112578810.3390/jpm12050788Pharmacogenetics of Donepezil and Memantine in Healthy SubjectsMaría C. Ovejero-Benito0Dolores Ochoa1Teresa Enrique-Benedito2Miriam del Peso-Casado3Pablo Zubiaur4Marcos Navares5Manuel Román6Francisco Abad-Santos7Clinical Pharmacology Department, Instituto de Investigación Sanitaria La Princesa (IP), Hospital Universitario de La Princesa, 28006 Madrid, SpainClinical Pharmacology Department, Instituto de Investigación Sanitaria La Princesa (IP), Hospital Universitario de La Princesa, 28006 Madrid, SpainClinical Pharmacology Department, Instituto de Investigación Sanitaria La Princesa (IP), Hospital Universitario de La Princesa, 28006 Madrid, SpainClinical Pharmacology Department, Instituto de Investigación Sanitaria La Princesa (IP), Hospital Universitario de La Princesa, 28006 Madrid, SpainClinical Pharmacology Department, Instituto de Investigación Sanitaria La Princesa (IP), Hospital Universitario de La Princesa, 28006 Madrid, SpainClinical Pharmacology Department, Instituto de Investigación Sanitaria La Princesa (IP), Hospital Universitario de La Princesa, 28006 Madrid, SpainClinical Pharmacology Department, Instituto de Investigación Sanitaria La Princesa (IP), Hospital Universitario de La Princesa, 28006 Madrid, SpainClinical Pharmacology Department, Instituto de Investigación Sanitaria La Princesa (IP), Hospital Universitario de La Princesa, 28006 Madrid, SpainDonepezil and memantine are the most common drugs used for Alzheimer’s disease. Their low effectiveness could partly be explained by genetic factors. Thus, we aim to identify Single Nucleotide Polymorphisms (SNPs) associated with pharmacokinetics, pharmacodynamics, and the safety of donepezil and memantine. For this regard, 25 volunteers enrolled in a bioequivalence clinical trial were genotyped for 67 SNPs in 21 genes with a ThermoFisher QuantStudio 12K Flex OpenArray. The statistical strategy included a univariate analysis that analyzed the association of these SNPs with pharmacokinetic parameters or the development of adverse drug reactions (ADRs) followed by a Bonferroni-corrected multivariate regression. Statistical analyses were performed with SPSS software v.21 and R commander (version v3.6.3). In the univariate analysis, fourteen and sixteen SNPs showed a significant association with memantine’s and donepezil’s pharmacokinetic parameters, respectively. Rs20417 (<i>PTGS2</i>) was associated with the development of at least one ADR. However, none of these associations reached the significance threshold in the Bonferroni-corrected multivariate analysis. In conclusion, we did not observe any significant association of the SNPs analyzed with memantine and donepezil pharmacokinetics or ADRs. Current evidence on memantine and donepezil pharmacogenetics does not justify their inclusion in pharmacogenetic guidelines.https://www.mdpi.com/2075-4426/12/5/788Alzheimerpharmacogenomicspharmacogenetic arraypharmacokineticsanticholinergic drugspersonalized medicine |
| spellingShingle | María C. Ovejero-Benito Dolores Ochoa Teresa Enrique-Benedito Miriam del Peso-Casado Pablo Zubiaur Marcos Navares Manuel Román Francisco Abad-Santos Pharmacogenetics of Donepezil and Memantine in Healthy Subjects Journal of Personalized Medicine Alzheimer pharmacogenomics pharmacogenetic array pharmacokinetics anticholinergic drugs personalized medicine |
| title | Pharmacogenetics of Donepezil and Memantine in Healthy Subjects |
| title_full | Pharmacogenetics of Donepezil and Memantine in Healthy Subjects |
| title_fullStr | Pharmacogenetics of Donepezil and Memantine in Healthy Subjects |
| title_full_unstemmed | Pharmacogenetics of Donepezil and Memantine in Healthy Subjects |
| title_short | Pharmacogenetics of Donepezil and Memantine in Healthy Subjects |
| title_sort | pharmacogenetics of donepezil and memantine in healthy subjects |
| topic | Alzheimer pharmacogenomics pharmacogenetic array pharmacokinetics anticholinergic drugs personalized medicine |
| url | https://www.mdpi.com/2075-4426/12/5/788 |
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