Merck
  • Home
  • Search Results
  • Paroxetine decreased plasma exposure of glyburide partly via inhibiting intestinal absorption in rats.

Paroxetine decreased plasma exposure of glyburide partly via inhibiting intestinal absorption in rats.

Drug metabolism and pharmacokinetics (2015-04-22)
Shuwen Jiang, Weiman Zhao, Yang Chen, Zeyu Zhong, Mian Zhang, Feng Li, Ping Xu, Kaijing Zhao, Ying Li, Li Liu, Xiaodong Liu
ABSTRACT

Accumulating evidences have shown that diabetes is often accompanied with depression, thus it is possible that oral antidiabetic agent glyburide and antidepressive agent paroxetine are co-administered in diabetic patients. The aim of this study was to assess interactions between glyburide and paroxetine in rats. Effect of paroxetine on pharmacokinetics of orally administered glyburide was investigated. Effect of naringin (NAR), an inhibitor of rat intestinal organic anion transporting polypeptides 1a5 (Oatp1a5), on pharmacokinetics of glyburide was also studied. The results showed that co-administration of paroxetine markedly reduced plasma exposure and prolonged Tmax of glyburide, accompanied by significant increase in fecal excretion of glyburide. Co-administration of naringin also significantly decreased plasma exposure of glyburide. Data from intestinal perfusion experiments showed that both paroxetine and naringin significantly inhibited intestinal absorption of glyburide. Caco-2 cells were used to investigate whether paroxetine and naringin affected intestinal transport of glyburide and fexofenadine (a substrate of Oatp1a5). The results showed that both paroxetine and naringin greatly inhibited absorption of glyburide and fexofenadine. All results gave a conclusion that co-administration of paroxetine decreased plasma exposure of glyburide in rats via inhibiting intestinal absorption of glyburide, which may partly be attributed to the inhibition of intestinal Oatp1a5 activity.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Glyburide, meets USP testing specifications
Sigma-Aldrich
Glybenclamide, ≥99% (HPLC)
Sigma-Aldrich
Naringin, ≥90%, from citrus fruit
Sigma-Aldrich
β-Nicotinamide adenine dinucleotide phosphate hydrate
Sigma-Aldrich
Naringin, ≥95% (HPLC)
Sigma-Aldrich
β-Nicotinamide adenine dinucleotide phosphate sodium salt, pkg of 5 mg (per vial)
Sigma-Aldrich
β-Nicotinamide adenine dinucleotide phosphate sodium salt, pkg of 10 mg (per vial)