Bibliographic Details
| Title: |
Effect of hesperetin on the pharmacokinetics of metoprolol succinate in rats |
| Authors: |
Ravindra Babu Pingili, Sridhar Vemulapalli, Surya Sandeep Mullapudi, Vijaya R. Dirisala, Harsha Sai Chanumolu, Naveen Babu Kilaru |
| Source: |
Future Journal of Pharmaceutical Sciences, Vol 9, Iss 1, Pp 1-8 (2023) |
| Publisher Information: |
SpringerOpen, 2023. |
| Publication Year: |
2023 |
| Collection: |
LCC:Therapeutics. Pharmacology
LCC:Pharmacy and materia medica |
| Subject Terms: |
Metoprolol, Hesperetin, CYP3A4, CYP2C9, P-glycoprotein, Therapeutics. Pharmacology, RM1-950, Pharmacy and materia medica, RS1-441 |
| More Details: |
Abstract Background Metoprolol is a substrate of CYP3A4, 2B6, CYP2D6, CYP2C9, and p-glycoprotein (p-gp). Hesperetin was reported as an inhibitor of cytochrome P-450 (CYP) enzymes and p-gp. The objective of this study was to investigate the effect of hesperetin on the pharmacokinetics of metoprolol in rats and in vitro models. In in vivo studies, male Wistar rats were treated with metoprolol (30 mg/kg) once a day for 15 consecutive days alone and in combination with hesperetin (25, 50, and 100 mg/kg). Blood samples were withdrawn from the tail vein on the 1st day in the single-dose pharmacokinetic study and on the 15th day in the repeated-dose pharmacokinetic study. In in vitro studies, metoprolol was incubated in the presence or absence of hesperetin and traditional p-gp inhibitors using rat-everted gut sacs. Reverse phase-high-performance liquid chromatography (RP-HPLC) was used to determine the amounts of metoprolol in the plasma and incubated samples (RP-HPLC). Results The C max, AUC, and half-life (t 1/2) of metoprolol significantly increased by twofold compared to the metoprolol group in rats pre-treated with hesperetin. The clearance and volume of distribution both decreased significantly. Metoprolol transport was dramatically increased in the presence of hesperetin and quinidine (standard p-gp inhibitor) in in vitro study. Conclusion The present study results revealed that hesperetin significantly increased the absorption of metoprolol in rats and everted gut sacs in vitro might be due to the inhibition of CYP and p-gp. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2314-7253 |
| Relation: |
https://doaj.org/toc/2314-7253 |
| DOI: |
10.1186/s43094-022-00457-x |
| Access URL: |
https://doaj.org/article/c5625190684e4e7998179bb52df98769 |
| Accession Number: |
edsdoj.5625190684e4e7998179bb52df98769 |
| Database: |
Directory of Open Access Journals |
