دورية أكاديمية
Impact of Sex and Genetic Variation in Relevant Pharmacogenes on the Pharmacokinetics and Safety of Valsartan, Olmesartan and Hydrochlorothiazide
| العنوان: | Impact of Sex and Genetic Variation in Relevant Pharmacogenes on the Pharmacokinetics and Safety of Valsartan, Olmesartan and Hydrochlorothiazide |
|---|---|
| المؤلفون: | Paula Soria-Chacartegui, Pablo Zubiaur, Dolores Ochoa, Marcos Navares-Gómez, Houwaida Abbes, Gonzalo Villapalos-García, Alejandro de Miguel, Eva González-Iglesias, Andrea Rodríguez-Lopez, Gina Mejía-Abril, Samuel Martín-Vilchez, Sergio Luquero-Bueno, Manuel Román, Francisco Abad-Santos |
| المصدر: | International Journal of Molecular Sciences, Vol 24, Iss 20, p 15265 (2023) |
| بيانات النشر: | MDPI AG, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Biology (General) LCC:Chemistry |
| مصطلحات موضوعية: | valsartan, olmesartan, hydrochlorothiazide, pharmacogenetics, ABCB1 and SLC22A1, Biology (General), QH301-705.5, Chemistry, QD1-999 |
| الوصف: | Drug combination therapy is the most common pharmacological strategy for hypertension management. No pharmacogenetic biomarkers for guiding hypertension pharmacotherapy are available to date. The study population were 64 volunteers from seven bioequivalence trials investigating formulations with valsartan, olmesartan and/or hydrochlorothiazide. Every volunteer was genotyped for 10 genetic variants in different transporters’ genes. Additionally, valsartan-treated volunteers were genotyped for 29 genetic variants in genes encoding for different metabolizing enzymes. Variability in pharmacokinetic parameters such as maximum concentration (Cmax) and time to reach it (tmax), the incidence of adverse drug reactions (ADRs) and blood pressure measurements were analyzed as a function of pharmacogenetic and demographic parameters. Individuals with the ABCB1 rs1045642 T/T genotype were associated with a higher valsartan tmax compared to those with T/G and G/G genotypes (p < 0.001, β = 0.821, R2 = 0.459) and with a tendency toward a higher postural dizziness incidence (11.8% vs. 0%, p = 0.070). A higher hydrochlorothiazide dose/weight (DW)-corrected area under the curve (AUC∞/DW) was observed in SLC22A1 rs34059508 G/A volunteers compared to G/G volunteers (p = 0.050, β = 1047.35, R2 = 0.051), and a tendency toward a higher postural dizziness incidence (50% vs. 1.6%, p = 0.063). Sex impacted valsartan and hydrochlorothiazide pharmacokinetics, showing a lower exposure in women, whereas no significant differences were found for olmesartan pharmacokinetics. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1422-0067 1661-6596 |
| Relation: | https://www.mdpi.com/1422-0067/24/20/15265; https://doaj.org/toc/1661-6596; https://doaj.org/toc/1422-0067 |
| DOI: | 10.3390/ijms242015265 |
| URL الوصول: | https://doaj.org/article/641dd31f467947ce9fa38ed9c2f37c9e |
| رقم الأكسشن: | edsdoj.641dd31f467947ce9fa38ed9c2f37c9e |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14220067 16616596 |
|---|---|
| DOI: | 10.3390/ijms242015265 |