Assessing CYP2C8-Mediated Pharmaceutical Excipient-Drug Interaction Potential: A Case Study of Tween 80 and Cremophor EL−35
| Autor: | Xin Liu, Ling Wang, Wenwen Zhang, Xuehua Jiang, Haoyang Hu, Chengming Wen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Drug
CYP2C8 Tween 80 enzyme inhibitory media_common.quotation_subject Pharmaceutical Science pharmaceutical excipients-drug interaction Pharmacology Pharmaceutical formulation Article chemistry.chemical_compound Pharmacy and materia medica In vivo EL−35 pharmaceutical excipients media_common Chemistry fungi food and beverages Transporter Drug interaction In vitro body regions RS1-441 Cyp2c22 Paclitaxel human activities |
| Zdroj: | Pharmaceutics, Vol 13, Iss 1492, p 1492 (2021) Pharmaceutics Volume 13 Issue 9 |
| ISSN: | 1999-4923 |
| Popis: | Pharmaceutical excipients (PEs) are substances included in drug formulations. Recent studies have revealed that some PEs can affect the activity of metabolic enzymes and drug transporters however, the effects of PEs on CYP2C8 and its interaction potential with drugs remain unclear. In this study, we evaluated the effects of Tween 80 and EL−35 on CYP2C8 in vitro and further investigated their impacts on the PK of paclitaxel (PTX) in rats after single or multiple doses. The in vitro study indicated that Tween 80 and EL−35 inhibited CYP2C8 activity in human and rat liver microsomes. EL−35 also decreased the expression of CYP2C8 in HepG2 cells. In the in vivo study, Tween 80 did not alter the PK of PTX after single or multiple doses, whereas EL−35 administered for 14 days significantly increased the AUC and MRT of PTX. Further analysis indicated that multiple-dose EL−35 reduced the expression of Cyp2c22 and production of 6-OH-PTX in the rat liver. Our study suggested that short-term exposure to both PEs did not affect the PK of PTX in rats, but multiple doses of EL−35 increased the AUC and MRT of PTX by downregulating the hepatic expression of Cyp2c22. Such effects should be taken into consideration during drug formulation and administration. |
| Databáze: | OpenAIRE |
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