Instant Access to the Journals You Need

for just $40 per month.

Start Your Free Trial

Investigation of the Inhibitory Effects of Various Drugs on the Hepatic Uptake of Fexofenadine in Humans

Investigation of the Inhibitory Effects of Various Drugs on the Hepatic Uptake of Fexofenadine in Humans

Abstract

Abstract Fexofenadine (FEX), an H 1 -receptor antagonist, is eliminated from the liver mainly in an unchanged form. Our previous study suggested that organic anion-transporting polypeptide (OATP) 1B3 contributes mainly to the hepatic uptake of FEX. On the other hand, a clinical report demonstrated that a T521C mutation of OATP1B1 increased its plasma area under the plasma concentration-time curve. Several compounds are reported to have a drug interaction with FEX, and some of this may be caused by the inhibition of its hepatic uptake. We determined which transporters are involved in the hepatobiliary transport of FEX by using double transfectants and examined whether clinically reported drug interactions with FEX could be explained by the inhibition of its hepatic uptake. Vectorial basal-to-apical transport of FEX was observed in double transfectants expressing OATP1B1/multidrug resistance-associated protein 2 (MRP2) and OATP1B3/MRP2, suggesting that OATP1B1 as well as OATP1B3 is involved in the hepatic uptake of FEX and that MRP2 can recognize FEX as a substrate. The inhibitory effects of compounds on FEX uptake in OATP1B3-expressing HEK293 cells were investigated, and the maximal degree of increase in plasma AUC of FEX by drug interaction in clinical situations was estimated. As a result, cyclosporin A and rifampicin were found to have the potential to interact with OATP1B3-mediated uptake at clinical concentrations. From these results, most of the reported drug interaction cannot be explained by the inhibition of hepatic uptake of FEX, and different mechanisms such as the inhibition of intestinal efflux should be considered.
Loading next page...
 
/lp/am-soc-for-pharma-experimental-therapeutics/investigation-of-the-inhibitory-effects-of-various-drugs-on-the-Ablx96raJc

You're reading a free preview. Subscribe to read the entire article.

And millions more from thousands of peer-reviewed journals, for only $40/month.

Start Your Free Trial

What content is in DeepDyve?

  • Read and share from thousands of the leading scholarly journals from Springer, Elsevier, Nature, IEEE, Wiley-Blackwell and more.
  • All the latest content is available, no embargo periods.

Rent Scholarly Articles?

  • Read the full article in your browser.
  • Access all of your rentals from the cloud anywhere you have an internet connection.
  • Beautiful reading experience – Full charts and figures, just like the PDF.
  • Read as much as you'd like - whenever you'd like.

Happy Users

“In one word renting from DeepDyve is FANTASTIC!!! ... 99% of the time I only need access to an article for a month or so, so renting the articles is perfect for me.”

Adam S.

“Thanks for a great service! For an unaffiliated science blogger like myself this is like a dream come true.”

Seppo P.

“Hi guys, I cannot tell you how much I love this resource. Incredible. I really believe you've hit the nail on the head with this site in regards to solving the research-purchase issue.”

Daniel C.

“Let me seize this opportunity and congratulate you on the service you are rendering to the scientific community.”

Joao B.