ROLE OF TRANSPORTERS IN TOXICOLOGY AND DRUG DEVELOPMENT
Most often experimental toxicologists are imbibed in routine OECD guideline testing which they consider as an end in all, which is far from the truth. To be a well-rounded and solid toxicologist, a firm grounding in pharmacokinetics, drug transporters, reaction phenotyping, drug-drug interaction etc., are integral to be a professional toxicologist.
Measurement of the potential of new drugs to be substrates or inhibitors of drug transporters is important in evaluating the safety of a drug in the preclinical development process, as well as to predict potential pharmacokinetic-based interactions with other medicines.
Drug transporters and drug-metabolizing enzymes participate in the processes of absorption, disposition, metabolism and elimination, which influence the pharmacokinetics and pharmacodynamics of a new chemical entity (NCE). Selective passage of molecules across the plasma membrane is controlled by transport proteins. Consequently, understanding the exact mechanisms of drug transporters is essential both in drug development and in drug therapy.
The predominant transporters involved in drug uptake are members of the solute carrier (SLC) transporter superfamily, which are located on the sinusoidal (basolateral) plasma membrane. In contrast, transporters responsible for the excretion of drugs and drug metabolites from hepatocytes belong to the ATP-binding cassette (ABC) transporter superfamily and are located on the biliary canalicular (apical) plasma membrane, where they mediate the excretion of drugs into bile, or on the sinusoidal membrane, where they mediate efflux back into the circulation. Based on the direction, the transporter can be categorized into influx or efflux transporters.
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Non-clinical, regulatory strategy and risk assessment
6 年Very informative
Subject Matter Expert - Safety Assessment, Eurofins Advinus
6 年Thank you all.? I will work on other topics (including neonatal toxicology - Vijay Malshetty), since two others are in the pipeline.
Pharmacist Toxicologist
6 年Very interesting work! Congrats and good luck
Consultant Toxicologist (Freelance)
6 年Gave it one reading early in the morning. Concise and simple. Excellent work sir!
Vice-Chancellor, Dean & Professor Dept. of Zoology, Vijayanagara Sri Krishnadevaraya University, Ballari
6 年My dear Sir! Thank you for a very interesting and informative article...I hope next article will be on juvenile??