Pharmacokinetic study on the interaction between succinic acid and irbesartan in rats and its potential mechanism
Context Succinic acid and irbesartan are commonly used drugs in cardiovascular disease treatment. The interaction might occur during their co-administration, which was still unclear. Objective To reveal the effect of succinic acid on the metabolism of irbesartan and its potential mechanism. Material...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2021-01-01
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| Series: | Pharmaceutical Biology |
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| Online Access: | http://dx.doi.org/10.1080/13880209.2021.2002370 |
| _version_ | 1819036682672930816 |
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| author | Yongpeng Wang Ruping Rui Xiaoyan Zhang Bin Sun |
| author_facet | Yongpeng Wang Ruping Rui Xiaoyan Zhang Bin Sun |
| author_sort | Yongpeng Wang |
| collection | DOAJ |
| description | Context Succinic acid and irbesartan are commonly used drugs in cardiovascular disease treatment. The interaction might occur during their co-administration, which was still unclear. Objective To reveal the effect of succinic acid on the metabolism of irbesartan and its potential mechanism. Materials and methods The Sprague-Dawley rats (n = 6) were treated with a single dose of 30 mg/kg irbesartan (control) or the co-administration with the pre-treatment of 200 mg/kg succinic acid for 7 d. The effect of succinic acid on the metabolic stability and the activity of CYP2C9 was evaluated in rat liver microsomes. Results Succinic acid increased the AUC (5328.71 ± 959.31 μg/L × h vs. 3340.23 ± 737.75 μg/L × h) and prolonged the half-life of irbesartan (from 12.79 ± 0.73 h to 20.59 ± 6.35 h). The Tmax (2.83 ± 0.75 h vs. 3.83 ± 1.10 h) and clearance rate (3.46 ± 1.13 L/h/kg vs. 6.91 ± 1.65 L/h/kg) of irbesartan was reduced by succinic acid. Consistently, succinic acid improved the metabolic stability (half-life from 23.32 ± 3.46 to 27.35 ± 2.15 min, intrinsic clearance rate from 59.43 ± 6.12 to 50.68 ± 5.64 μL/min/mg protein). Succinic acid was also found to inhibit the activity of CYP2C9 with the IC50 value of 13.87 μM. Discussion and conclusions Succinic acid increased the system exposure of irbesartan via inhibiting CYP2C9. The experiment design of this study also provides a reference for the further validation of this interaction in humans. |
| first_indexed | 2024-12-21T08:09:24Z |
| format | Article |
| id | doaj.art-b85959821d584688b6004bc9ae771af7 |
| institution | Directory Open Access Journal |
| issn | 1388-0209 1744-5116 |
| language | English |
| last_indexed | 2024-12-21T08:09:24Z |
| publishDate | 2021-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Pharmaceutical Biology |
| spelling | doaj.art-b85959821d584688b6004bc9ae771af72022-12-21T19:10:43ZengTaylor & Francis GroupPharmaceutical Biology1388-02091744-51162021-01-015911619162210.1080/13880209.2021.20023702002370Pharmacokinetic study on the interaction between succinic acid and irbesartan in rats and its potential mechanismYongpeng Wang0Ruping Rui1Xiaoyan Zhang2Bin Sun3Department of Cardiovascular Medicine, Yidu Central Hospital of WeifangDepartment of Cardiovascular Medicine, Yidu Central Hospital of WeifangQingzhou Tanfang Town Central Health CenterDepartment of Emergency, Yidu Central Hospital of WeifangContext Succinic acid and irbesartan are commonly used drugs in cardiovascular disease treatment. The interaction might occur during their co-administration, which was still unclear. Objective To reveal the effect of succinic acid on the metabolism of irbesartan and its potential mechanism. Materials and methods The Sprague-Dawley rats (n = 6) were treated with a single dose of 30 mg/kg irbesartan (control) or the co-administration with the pre-treatment of 200 mg/kg succinic acid for 7 d. The effect of succinic acid on the metabolic stability and the activity of CYP2C9 was evaluated in rat liver microsomes. Results Succinic acid increased the AUC (5328.71 ± 959.31 μg/L × h vs. 3340.23 ± 737.75 μg/L × h) and prolonged the half-life of irbesartan (from 12.79 ± 0.73 h to 20.59 ± 6.35 h). The Tmax (2.83 ± 0.75 h vs. 3.83 ± 1.10 h) and clearance rate (3.46 ± 1.13 L/h/kg vs. 6.91 ± 1.65 L/h/kg) of irbesartan was reduced by succinic acid. Consistently, succinic acid improved the metabolic stability (half-life from 23.32 ± 3.46 to 27.35 ± 2.15 min, intrinsic clearance rate from 59.43 ± 6.12 to 50.68 ± 5.64 μL/min/mg protein). Succinic acid was also found to inhibit the activity of CYP2C9 with the IC50 value of 13.87 μM. Discussion and conclusions Succinic acid increased the system exposure of irbesartan via inhibiting CYP2C9. The experiment design of this study also provides a reference for the further validation of this interaction in humans.http://dx.doi.org/10.1080/13880209.2021.2002370cardiovascular diseasedrug–drug interactioncyp2c9amber |
| spellingShingle | Yongpeng Wang Ruping Rui Xiaoyan Zhang Bin Sun Pharmacokinetic study on the interaction between succinic acid and irbesartan in rats and its potential mechanism Pharmaceutical Biology cardiovascular disease drug–drug interaction cyp2c9 amber |
| title | Pharmacokinetic study on the interaction between succinic acid and irbesartan in rats and its potential mechanism |
| title_full | Pharmacokinetic study on the interaction between succinic acid and irbesartan in rats and its potential mechanism |
| title_fullStr | Pharmacokinetic study on the interaction between succinic acid and irbesartan in rats and its potential mechanism |
| title_full_unstemmed | Pharmacokinetic study on the interaction between succinic acid and irbesartan in rats and its potential mechanism |
| title_short | Pharmacokinetic study on the interaction between succinic acid and irbesartan in rats and its potential mechanism |
| title_sort | pharmacokinetic study on the interaction between succinic acid and irbesartan in rats and its potential mechanism |
| topic | cardiovascular disease drug–drug interaction cyp2c9 amber |
| url | http://dx.doi.org/10.1080/13880209.2021.2002370 |
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