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Molecular Mechanisms for Species Differences in Organic Anion Transporter 1, OAT1: Implications for Renal Drug Toxicity.

Author: ChienHuan-Chieh, FennerKatherine S, GiacominiKathleen M, GuptaAnshul, PrasadBhagwat, StahlSimone H, SteculaAdrian, UnadkatJashvant D, WangLi, YeeSook Wah, ZouLing

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Overview

This study investigated the species differences in renal drug transport of acyclic nucleoside phosphonates (ANPs). The research identified serine at position 203 (S203) in human OAT1 as a crucial factor for its lower Km value compared to animal models. This finding provides insights into the species-specific renal accumulation of nephrotoxic ANPs and OAT1 transport function in primate evolution.
Paper Details　
Original Abstract of the Article :
Species differences in renal drug transporters continue to plague drug development with animal models failing to adequately predict renal drug toxicity. For example, adefovir, a renally excreted antiviral drug, failed clinical studies for human immunodeficiency virus due to pronounced nephrotoxicity...See full text at original site
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引用元：
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5987998/

データ提供：米国国立医学図書館（NLM）

Unveiling Species Differences in Organic Anion Transporter 1: Implications for Renal Drug Toxicity

Species differences in renal drug transporters often pose significant challenges in drug development, making it difficult to accurately predict drug toxicity in humans based on animal models. This study investigates the molecular mechanisms underlying species differences in the organic anion transporter 1 (OAT1), a critical transporter for renal drug excretion. The researchers identified a key amino acid residue responsible for differences in the transport kinetics of acyclic nucleoside phosphonates (ANPs), a class of antiviral drugs, in different species. Their findings suggest that these species differences could explain discrepancies in renal drug toxicity observed in humans and animal models.

OAT1: A Molecular Key to Understanding Renal Drug Toxicity

This research provides valuable insights into the molecular mechanisms governing renal drug transport, helping to explain the differences in drug toxicity observed across species. The study's findings could lead to improved drug development strategies and more accurate predictions of drug toxicity in humans.

From Animal Models to Human Health: Bridging the Gap in Drug Development

The study emphasizes the importance of understanding species differences in drug transport mechanisms to develop more effective and safer drugs for human use. By bridging the gap between animal models and human responses, researchers can pave the way for more personalized and effective drug therapies.

Dr. Camel's Conclusion

Just as a camel adapts to survive in different desert ecosystems, researchers are exploring the diverse ways in which drugs interact with different species. This study highlights the importance of understanding species differences in renal drug transporters, a crucial step in developing safe and effective medications for human use. By navigating the complexities of drug transport mechanisms, researchers can pave the way for more precise and personalized drug therapies.

Date :
  1. Date Completed 2019-02-22
  2. Date Revised 2019-07-01
Further Info :

Pubmed ID

29720497

DOI: Digital Object Identifier

PMC5987998

Related Literature

Article Analysis
・Side Effects of adefovir
SNS
PICO Info
in preparation
Languages

English

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