کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5849372 | 1561750 | 2016 | 10 صفحه PDF | دانلود رایگان |

- Steviol acyl glucuronide (SVAG) is a reversible inhibitor of CYP2C8 with a Ki of 13.9 μM.
- SVAG inhibited repaglinide 3â²-hydroxylation (a CYP2C8 probe reaction) both in HLM and rhCYP2C8 systems.
- After an oral administration of rebaudioside A, SVAG showed a high liver to plasma ratio (up to 25.5) in rats.
- SVAG did not inhibit repaglinide 3â²-hydroxylation in rats, suggesting a species difference.
- Prediction using available human data suggests a moderate interaction potential between repaglinide and SVAG.
CYP2C8 is involved in the metabolic clearance of several important drugs and recent reports have shown that acyl glucuronides of gemfibrozil and clopidogrel are potent time-dependent inhibitors of CYP2C8 activity. In the present study, the inhibitory effect of steviol acyl glucuronide (SVAG), a circulating metabolite formed after the ingestion of rebaudioside A, was investigated using in vitro and in vivo systems. Results indicated that SVAG was a reversible but not a time-dependent inhibitor of CYP2C8-mediated paclitaxel 6α-hydroxylation. SVAG was also capable of inhibiting CYP2C8-mediated repaglinide 3â²-hydroxylation in human liver microsomes and recombinant human CYP2C8, with Ki values of 15.8 μM and 11.6 μM, respectively. In contrast, SVAG did not exhibit inhibitory effect on CYP2C8 activity in rat liver microsomes. In addition, co-administration of rebaudioside A with repaglinide in rats did not lead to AUC and Cmax changes of repaglinide. Although mathematic prediction using a simplified mechanistic model revealed a moderate interaction potential between repaglinide and SVAG, cautions should be given to patients with hypoglycemia if repaglinide and rebaudioside A are used in combination for the blood sugar control.
Journal: Food and Chemical Toxicology - Volume 94, August 2016, Pages 138-147