Pharmacokinetic interaction study between ligustrazine and valsartan in rats and its potential mechanism
Context Ligustrazine and valsartan are commonly used drugs in the treatment of cardiac and cardiovascular disease. Objective The interaction between ligustrazine and valsartan was studied to investigate the effect of ligustrazine on the pharmacokinetics of valsartan. Materials and methods The pharma...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2020-01-01
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| Series: | Pharmaceutical Biology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/13880209.2020.1859554 |
| _version_ | 1818449571762667520 |
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| author | Yang Liu Jiaqi Zhang Di Wu Liran Cui |
| author_facet | Yang Liu Jiaqi Zhang Di Wu Liran Cui |
| author_sort | Yang Liu |
| collection | DOAJ |
| description | Context Ligustrazine and valsartan are commonly used drugs in the treatment of cardiac and cardiovascular disease. Objective The interaction between ligustrazine and valsartan was studied to investigate the effect of ligustrazine on the pharmacokinetics of valsartan. Materials and methods The pharmacokinetics of valsartan (10 mg/kg) was investigated in Sprague–Dawley rats divided into three groups (with the pretreatment of 4 or 10 mg/kg/day ligustrazine for 10 days and without the pretreatment of ligustrazine as control) of six rats each. The in vitro experiments in rat liver microsomes were performed to explore the effect of ligustrazine on the metabolic stability of valsartan. Results Ligustrazine changed the pharmacokinetic profile of valsartan. In the presence of 4 mg/kg ligustrazine, the AUC(0–t) (385.37 ± 93.05 versus 851.64 ± 104.26 μg/L*h), t1/2 (5.46 ± 0.93 versus 6.34 ± 1.25 h), and Cmax (62.64 ± 9.09 versus 83.87 ± 6.15 μg/L) of valsartan was significantly decreased, and the clearance rate was increased from 10.92 ± 1.521 to 25.76 ± 6.24 L/h/kg and similar changes were observed in the group with 10 mg/kg ligustrazine (p < 0.05). The metabolic stability of valsartan was also decreased by ligustrazine as the half-life of valsartan in rat liver microsomes decreased from 37.12 ± 4.06 to 33.48 ± 3.56 min and the intrinsic clearance rate increased from 37.34 ± 3.84 to 41.40 ± 4.32 μL/min/mg protein (p < 0.05). Discussion and conclusions Ligustrazine promoted the metabolism of valsartan via activating CYP3A4. The co-administration of ligustrazine and valsartan should be taken into account. |
| first_indexed | 2024-12-14T20:37:32Z |
| format | Article |
| id | doaj.art-80b63fcfa6e74c19a545d16f284bce77 |
| institution | Directory Open Access Journal |
| issn | 1388-0209 1744-5116 |
| language | English |
| last_indexed | 2024-12-14T20:37:32Z |
| publishDate | 2020-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Pharmaceutical Biology |
| spelling | doaj.art-80b63fcfa6e74c19a545d16f284bce772022-12-21T22:48:21ZengTaylor & Francis GroupPharmaceutical Biology1388-02091744-51162020-01-015811299130210.1080/13880209.2020.18595541859554Pharmacokinetic interaction study between ligustrazine and valsartan in rats and its potential mechanismYang Liu0Jiaqi Zhang1Di Wu2Liran Cui3Department of Pharmacy, The First Affiliated Hospital of Qiqihar Medical University, Fularji DistrictDepartment of Pharmacy, The First Affiliated Hospital of Qiqihar Medical University, Fularji DistrictCentral Laboratory, The First Affiliated Hospital of Qiqihar Medical University, Fularji DistrictCentral Laboratory, The First Affiliated Hospital of Qiqihar Medical University, Fularji DistrictContext Ligustrazine and valsartan are commonly used drugs in the treatment of cardiac and cardiovascular disease. Objective The interaction between ligustrazine and valsartan was studied to investigate the effect of ligustrazine on the pharmacokinetics of valsartan. Materials and methods The pharmacokinetics of valsartan (10 mg/kg) was investigated in Sprague–Dawley rats divided into three groups (with the pretreatment of 4 or 10 mg/kg/day ligustrazine for 10 days and without the pretreatment of ligustrazine as control) of six rats each. The in vitro experiments in rat liver microsomes were performed to explore the effect of ligustrazine on the metabolic stability of valsartan. Results Ligustrazine changed the pharmacokinetic profile of valsartan. In the presence of 4 mg/kg ligustrazine, the AUC(0–t) (385.37 ± 93.05 versus 851.64 ± 104.26 μg/L*h), t1/2 (5.46 ± 0.93 versus 6.34 ± 1.25 h), and Cmax (62.64 ± 9.09 versus 83.87 ± 6.15 μg/L) of valsartan was significantly decreased, and the clearance rate was increased from 10.92 ± 1.521 to 25.76 ± 6.24 L/h/kg and similar changes were observed in the group with 10 mg/kg ligustrazine (p < 0.05). The metabolic stability of valsartan was also decreased by ligustrazine as the half-life of valsartan in rat liver microsomes decreased from 37.12 ± 4.06 to 33.48 ± 3.56 min and the intrinsic clearance rate increased from 37.34 ± 3.84 to 41.40 ± 4.32 μL/min/mg protein (p < 0.05). Discussion and conclusions Ligustrazine promoted the metabolism of valsartan via activating CYP3A4. The co-administration of ligustrazine and valsartan should be taken into account.http://dx.doi.org/10.1080/13880209.2020.1859554metabolic stabilitycyp3a4metabolismdrug–drug interaction |
| spellingShingle | Yang Liu Jiaqi Zhang Di Wu Liran Cui Pharmacokinetic interaction study between ligustrazine and valsartan in rats and its potential mechanism Pharmaceutical Biology metabolic stability cyp3a4 metabolism drug–drug interaction |
| title | Pharmacokinetic interaction study between ligustrazine and valsartan in rats and its potential mechanism |
| title_full | Pharmacokinetic interaction study between ligustrazine and valsartan in rats and its potential mechanism |
| title_fullStr | Pharmacokinetic interaction study between ligustrazine and valsartan in rats and its potential mechanism |
| title_full_unstemmed | Pharmacokinetic interaction study between ligustrazine and valsartan in rats and its potential mechanism |
| title_short | Pharmacokinetic interaction study between ligustrazine and valsartan in rats and its potential mechanism |
| title_sort | pharmacokinetic interaction study between ligustrazine and valsartan in rats and its potential mechanism |
| topic | metabolic stability cyp3a4 metabolism drug–drug interaction |
| url | http://dx.doi.org/10.1080/13880209.2020.1859554 |
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