Exploring the Effect of Compound Glycyrrhizin and Silybinin on the Metabolism of Pexidartinib in Rats Based on CYP3A4 and CYP2C9
Pexidartinib offered a new therapeutic option for adult patients with symptomatic tenosynovial giant cell tumor (TGCT) who were refractory to surgical treatment and had severe morbidity or functional limitations. Meanwhile, the metabolism of pexidartinib was mainly mediated through the oxidation of...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Hindawi Limited
2023-01-01
|
| Series: | Advances in Pharmacological and Pharmaceutical Sciences |
| Online Access: | http://dx.doi.org/10.1155/2023/6737062 |
| _version_ | 1827009320502427648 |
|---|---|
| author | Yanding Su Xinyi Wei Qian Cheng He Qi Jianghui Chen Xiang-Jun Qiu |
| author_facet | Yanding Su Xinyi Wei Qian Cheng He Qi Jianghui Chen Xiang-Jun Qiu |
| author_sort | Yanding Su |
| collection | DOAJ |
| description | Pexidartinib offered a new therapeutic option for adult patients with symptomatic tenosynovial giant cell tumor (TGCT) who were refractory to surgical treatment and had severe morbidity or functional limitations. Meanwhile, the metabolism of pexidartinib was mainly mediated through the oxidation of cytochrome P450 (CYP) 3A and glucuronidation by uridine glucuronosyltransferase (UGT) 1A4 and attention shall be paid to CYP450-based drug-drug interactions during therapeutic dosing. This study aimed to examine the changes in the pharmacokinetics of pexidartinib by silymarin and compound glycyrrhizin on pexidartinib in vivo in rats by high-performance liquid chromatography (HPLC)-UV approach and to detect its expression in CYP3A4 and CYP2C9 using the western blot. The findings of chromatography experiments revealed that silybinin as well as compound glycyrrhizin increased the exposure of pexidartinib in rats and had a significant inhibitory effect on the metabolism of pexidartinib. The results of immunoblotting assays suggested that silybinin as well as compound glycyrrhizin inhibited the protein expression of CYP3A4 and CYP2C9 in rats. Therefore, the combination of pexidartinib with silybinin and compound glycyrrhizin should be monitored to avoid clinical adverse effects. |
| first_indexed | 2024-03-09T01:37:20Z |
| format | Article |
| id | doaj.art-95f4f67c9d054d1b9fdf4daa7596a296 |
| institution | Directory Open Access Journal |
| issn | 2633-4690 |
| language | English |
| last_indexed | 2025-02-18T12:46:15Z |
| publishDate | 2023-01-01 |
| publisher | Hindawi Limited |
| record_format | Article |
| series | Advances in Pharmacological and Pharmaceutical Sciences |
| spelling | doaj.art-95f4f67c9d054d1b9fdf4daa7596a2962024-11-02T03:59:26ZengHindawi LimitedAdvances in Pharmacological and Pharmaceutical Sciences2633-46902023-01-01202310.1155/2023/6737062Exploring the Effect of Compound Glycyrrhizin and Silybinin on the Metabolism of Pexidartinib in Rats Based on CYP3A4 and CYP2C9Yanding Su0Xinyi Wei1Qian Cheng2He Qi3Jianghui Chen4Xiang-Jun Qiu5College of Basic Medicine and Forensic MedicineCollege of Basic Medicine and Forensic MedicineCollege of Basic Medicine and Forensic MedicineCollege of Basic Medicine and Forensic MedicineCollege of Basic Medicine and Forensic MedicineCollege of Basic Medicine and Forensic MedicinePexidartinib offered a new therapeutic option for adult patients with symptomatic tenosynovial giant cell tumor (TGCT) who were refractory to surgical treatment and had severe morbidity or functional limitations. Meanwhile, the metabolism of pexidartinib was mainly mediated through the oxidation of cytochrome P450 (CYP) 3A and glucuronidation by uridine glucuronosyltransferase (UGT) 1A4 and attention shall be paid to CYP450-based drug-drug interactions during therapeutic dosing. This study aimed to examine the changes in the pharmacokinetics of pexidartinib by silymarin and compound glycyrrhizin on pexidartinib in vivo in rats by high-performance liquid chromatography (HPLC)-UV approach and to detect its expression in CYP3A4 and CYP2C9 using the western blot. The findings of chromatography experiments revealed that silybinin as well as compound glycyrrhizin increased the exposure of pexidartinib in rats and had a significant inhibitory effect on the metabolism of pexidartinib. The results of immunoblotting assays suggested that silybinin as well as compound glycyrrhizin inhibited the protein expression of CYP3A4 and CYP2C9 in rats. Therefore, the combination of pexidartinib with silybinin and compound glycyrrhizin should be monitored to avoid clinical adverse effects.http://dx.doi.org/10.1155/2023/6737062 |
| spellingShingle | Yanding Su Xinyi Wei Qian Cheng He Qi Jianghui Chen Xiang-Jun Qiu Exploring the Effect of Compound Glycyrrhizin and Silybinin on the Metabolism of Pexidartinib in Rats Based on CYP3A4 and CYP2C9 Advances in Pharmacological and Pharmaceutical Sciences |
| title | Exploring the Effect of Compound Glycyrrhizin and Silybinin on the Metabolism of Pexidartinib in Rats Based on CYP3A4 and CYP2C9 |
| title_full | Exploring the Effect of Compound Glycyrrhizin and Silybinin on the Metabolism of Pexidartinib in Rats Based on CYP3A4 and CYP2C9 |
| title_fullStr | Exploring the Effect of Compound Glycyrrhizin and Silybinin on the Metabolism of Pexidartinib in Rats Based on CYP3A4 and CYP2C9 |
| title_full_unstemmed | Exploring the Effect of Compound Glycyrrhizin and Silybinin on the Metabolism of Pexidartinib in Rats Based on CYP3A4 and CYP2C9 |
| title_short | Exploring the Effect of Compound Glycyrrhizin and Silybinin on the Metabolism of Pexidartinib in Rats Based on CYP3A4 and CYP2C9 |
| title_sort | exploring the effect of compound glycyrrhizin and silybinin on the metabolism of pexidartinib in rats based on cyp3a4 and cyp2c9 |
| url | http://dx.doi.org/10.1155/2023/6737062 |
| work_keys_str_mv | AT yandingsu exploringtheeffectofcompoundglycyrrhizinandsilybininonthemetabolismofpexidartinibinratsbasedoncyp3a4andcyp2c9 AT xinyiwei exploringtheeffectofcompoundglycyrrhizinandsilybininonthemetabolismofpexidartinibinratsbasedoncyp3a4andcyp2c9 AT qiancheng exploringtheeffectofcompoundglycyrrhizinandsilybininonthemetabolismofpexidartinibinratsbasedoncyp3a4andcyp2c9 AT heqi exploringtheeffectofcompoundglycyrrhizinandsilybininonthemetabolismofpexidartinibinratsbasedoncyp3a4andcyp2c9 AT jianghuichen exploringtheeffectofcompoundglycyrrhizinandsilybininonthemetabolismofpexidartinibinratsbasedoncyp3a4andcyp2c9 AT xiangjunqiu exploringtheeffectofcompoundglycyrrhizinandsilybininonthemetabolismofpexidartinibinratsbasedoncyp3a4andcyp2c9 |