Modeling the Influence of <i>CYP2C9</i> and <i>ABCB1</i> Gene Polymorphisms on the Pharmacokinetics and Pharmacodynamics of Losartan
<b>Background/Objectives:</b> Hypertension is a pathological condition characterized by elevated systolic and/or diastolic blood pressure. A range of pharmacotherapeutic agents are available to treat this condition and prevent complications, including the angiotensin II AT1-receptor bloc...
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2025-07-01
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| author | Dmitry Babaev Elena Kutumova Fedor Kolpakov |
| author_facet | Dmitry Babaev Elena Kutumova Fedor Kolpakov |
| author_sort | Dmitry Babaev |
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| description | <b>Background/Objectives:</b> Hypertension is a pathological condition characterized by elevated systolic and/or diastolic blood pressure. A range of pharmacotherapeutic agents are available to treat this condition and prevent complications, including the angiotensin II AT1-receptor blocker losartan. Following oral administration, losartan is exposed to a variety of enzymes that facilitate its metabolism or transportation. The structural characteristics of the genes that encode the enzymes may potentially impact the pharmacokinetics and pharmacodynamics of losartan, thereby modulating its effects on the treatment process. <b>Methods</b>: In this study, a computational model of losartan pharmacokinetics was developed, taking into account the influence of different alleles of the <i>CYP2C9</i> gene, which plays a pivotal role in losartan metabolism, and the <i>ABCB1</i> gene, which is responsible for losartan transport. <b>Results</b>: Alterations in the modeled activities of the enzymes encoded by <i>CYP2C9</i> and <i>ABCB1</i> result in changes in the losartan and its metabolite profiles that are consistent with known experimental data in real patients with different <i>CYP2C9</i> and <i>ABCB1</i> genotypes. <b>Conclusions</b>: The findings of the modeling can potentially be used to personalize drug therapy for arterial hypertension. |
| format | Article |
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| institution | Kabale University |
| issn | 1999-4923 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj-art-add4088ae5584a60892c911a1f2cb9bc2025-08-20T03:56:46ZengMDPI AGPharmaceutics1999-49232025-07-0117793510.3390/pharmaceutics17070935Modeling the Influence of <i>CYP2C9</i> and <i>ABCB1</i> Gene Polymorphisms on the Pharmacokinetics and Pharmacodynamics of LosartanDmitry Babaev0Elena Kutumova1Fedor Kolpakov2Department of Computational Biology, Sirius University of Science and Technology, 354340 Sirius, RussiaDepartment of Computational Biology, Sirius University of Science and Technology, 354340 Sirius, RussiaDepartment of Computational Biology, Sirius University of Science and Technology, 354340 Sirius, Russia<b>Background/Objectives:</b> Hypertension is a pathological condition characterized by elevated systolic and/or diastolic blood pressure. A range of pharmacotherapeutic agents are available to treat this condition and prevent complications, including the angiotensin II AT1-receptor blocker losartan. Following oral administration, losartan is exposed to a variety of enzymes that facilitate its metabolism or transportation. The structural characteristics of the genes that encode the enzymes may potentially impact the pharmacokinetics and pharmacodynamics of losartan, thereby modulating its effects on the treatment process. <b>Methods</b>: In this study, a computational model of losartan pharmacokinetics was developed, taking into account the influence of different alleles of the <i>CYP2C9</i> gene, which plays a pivotal role in losartan metabolism, and the <i>ABCB1</i> gene, which is responsible for losartan transport. <b>Results</b>: Alterations in the modeled activities of the enzymes encoded by <i>CYP2C9</i> and <i>ABCB1</i> result in changes in the losartan and its metabolite profiles that are consistent with known experimental data in real patients with different <i>CYP2C9</i> and <i>ABCB1</i> genotypes. <b>Conclusions</b>: The findings of the modeling can potentially be used to personalize drug therapy for arterial hypertension.https://www.mdpi.com/1999-4923/17/7/935arterial hypertensionlosartanpharmacokineticspharmacodynamics<i>ABCB1</i><i>CYP2C9</i> |
| spellingShingle | Dmitry Babaev Elena Kutumova Fedor Kolpakov Modeling the Influence of <i>CYP2C9</i> and <i>ABCB1</i> Gene Polymorphisms on the Pharmacokinetics and Pharmacodynamics of Losartan Pharmaceutics arterial hypertension losartan pharmacokinetics pharmacodynamics <i>ABCB1</i> <i>CYP2C9</i> |
| title | Modeling the Influence of <i>CYP2C9</i> and <i>ABCB1</i> Gene Polymorphisms on the Pharmacokinetics and Pharmacodynamics of Losartan |
| title_full | Modeling the Influence of <i>CYP2C9</i> and <i>ABCB1</i> Gene Polymorphisms on the Pharmacokinetics and Pharmacodynamics of Losartan |
| title_fullStr | Modeling the Influence of <i>CYP2C9</i> and <i>ABCB1</i> Gene Polymorphisms on the Pharmacokinetics and Pharmacodynamics of Losartan |
| title_full_unstemmed | Modeling the Influence of <i>CYP2C9</i> and <i>ABCB1</i> Gene Polymorphisms on the Pharmacokinetics and Pharmacodynamics of Losartan |
| title_short | Modeling the Influence of <i>CYP2C9</i> and <i>ABCB1</i> Gene Polymorphisms on the Pharmacokinetics and Pharmacodynamics of Losartan |
| title_sort | modeling the influence of i cyp2c9 i and i abcb1 i gene polymorphisms on the pharmacokinetics and pharmacodynamics of losartan |
| topic | arterial hypertension losartan pharmacokinetics pharmacodynamics <i>ABCB1</i> <i>CYP2C9</i> |
| url | https://www.mdpi.com/1999-4923/17/7/935 |
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