Effect of quercetin on the pharmacokinetics of selexipag and its active metabolite in beagles
Context As an inhibitor cytochrome P450 family 2 subfamily C polypeptide 8 (CYP2C8), quercetin is a naturally occurring flavonoid with its glycosides consumed at least 100 mg per day in food. However, it is still unknown whether quercetin and selexipag interact. Objective The study investigated the...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-01-01
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| Series: | Pharmaceutical Biology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/13880209.2021.2005636 |
| _version_ | 1818700110546075648 |
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| author | Shun-bin Luo Er-min Gu Yu-ao Chen Shi-chen Zhou Chen Fan Ren-ai Xu |
| author_facet | Shun-bin Luo Er-min Gu Yu-ao Chen Shi-chen Zhou Chen Fan Ren-ai Xu |
| author_sort | Shun-bin Luo |
| collection | DOAJ |
| description | Context As an inhibitor cytochrome P450 family 2 subfamily C polypeptide 8 (CYP2C8), quercetin is a naturally occurring flavonoid with its glycosides consumed at least 100 mg per day in food. However, it is still unknown whether quercetin and selexipag interact. Objective The study investigated the effect of quercetin on the pharmacokinetics of selexipag and ACT-333679 in beagles. Materials and methods The ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to investigate the pharmacokinetics of orally administered selexipag (2 mg/kg) with and without quercetin (2 mg/kg/day for 7 days) pre-treatment in beagles. The effect of quercetin on the pharmacokinetics of selexipag and its potential mechanism was studied through the pharmacokinetic parameters. Results The assay method was validated for selexipag and ACT-333679, and the lower limit of quantification for both was 1 ng/mL. The recovery and the matrix effect of selexipag were 84.5–91.58% and 94.98–99.67%, while for ACT-333679 were 81.21–93.90% and 93.17–99.23%. The UPLC-MS/MS method was sensitive, accurate and precise, and had been applied to the herb-drug interaction study of quercetin with selexipag and ACT-333679. Treatment with quercetin led to an increased in Cmax and AUC0–t of selexipag by about 43.08% and 26.92%, respectively. While the ACT-333679 was about 11.11% and 18.87%, respectively. Discussion and conclusion The study indicated that quercetin could inhibit the metabolism of selexipag and ACT-333679 when co-administration. Therefore, the clinical dose of selexipag should be used with caution when co-administered with foods high in quercetin. |
| first_indexed | 2024-12-17T14:59:44Z |
| format | Article |
| id | doaj.art-f1fc112475314ec0b9427a7556272fb3 |
| institution | Directory Open Access Journal |
| issn | 1388-0209 1744-5116 |
| language | English |
| last_indexed | 2024-12-17T14:59:44Z |
| publishDate | 2022-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Pharmaceutical Biology |
| spelling | doaj.art-f1fc112475314ec0b9427a7556272fb32022-12-21T21:43:56ZengTaylor & Francis GroupPharmaceutical Biology1388-02091744-51162022-01-016011810.1080/13880209.2021.20056362005636Effect of quercetin on the pharmacokinetics of selexipag and its active metabolite in beaglesShun-bin Luo0Er-min Gu1Yu-ao Chen2Shi-chen Zhou3Chen Fan4Ren-ai Xu5Department of Clinical Pharmacy, The People’s Hospital of LishuiDepartment of Pharmacy, The First People’s Hospital of JiashanSchool of Basic Medical Sciences, Henan University of Science and TechnologySchool of Basic Medical Sciences, Henan University of Science and TechnologySchool of Basic Medical Sciences, Henan University of Science and TechnologyDepartment of Pharmacy, The First Affiliated Hospital of Wenzhou Medical UniversityContext As an inhibitor cytochrome P450 family 2 subfamily C polypeptide 8 (CYP2C8), quercetin is a naturally occurring flavonoid with its glycosides consumed at least 100 mg per day in food. However, it is still unknown whether quercetin and selexipag interact. Objective The study investigated the effect of quercetin on the pharmacokinetics of selexipag and ACT-333679 in beagles. Materials and methods The ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to investigate the pharmacokinetics of orally administered selexipag (2 mg/kg) with and without quercetin (2 mg/kg/day for 7 days) pre-treatment in beagles. The effect of quercetin on the pharmacokinetics of selexipag and its potential mechanism was studied through the pharmacokinetic parameters. Results The assay method was validated for selexipag and ACT-333679, and the lower limit of quantification for both was 1 ng/mL. The recovery and the matrix effect of selexipag were 84.5–91.58% and 94.98–99.67%, while for ACT-333679 were 81.21–93.90% and 93.17–99.23%. The UPLC-MS/MS method was sensitive, accurate and precise, and had been applied to the herb-drug interaction study of quercetin with selexipag and ACT-333679. Treatment with quercetin led to an increased in Cmax and AUC0–t of selexipag by about 43.08% and 26.92%, respectively. While the ACT-333679 was about 11.11% and 18.87%, respectively. Discussion and conclusion The study indicated that quercetin could inhibit the metabolism of selexipag and ACT-333679 when co-administration. Therefore, the clinical dose of selexipag should be used with caution when co-administered with foods high in quercetin.http://dx.doi.org/10.1080/13880209.2021.2005636cyp2c8act-333679uplc-ms/msinhibitmetabolism |
| spellingShingle | Shun-bin Luo Er-min Gu Yu-ao Chen Shi-chen Zhou Chen Fan Ren-ai Xu Effect of quercetin on the pharmacokinetics of selexipag and its active metabolite in beagles Pharmaceutical Biology cyp2c8 act-333679 uplc-ms/ms inhibit metabolism |
| title | Effect of quercetin on the pharmacokinetics of selexipag and its active metabolite in beagles |
| title_full | Effect of quercetin on the pharmacokinetics of selexipag and its active metabolite in beagles |
| title_fullStr | Effect of quercetin on the pharmacokinetics of selexipag and its active metabolite in beagles |
| title_full_unstemmed | Effect of quercetin on the pharmacokinetics of selexipag and its active metabolite in beagles |
| title_short | Effect of quercetin on the pharmacokinetics of selexipag and its active metabolite in beagles |
| title_sort | effect of quercetin on the pharmacokinetics of selexipag and its active metabolite in beagles |
| topic | cyp2c8 act-333679 uplc-ms/ms inhibit metabolism |
| url | http://dx.doi.org/10.1080/13880209.2021.2005636 |
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