Interindividual differences in drug interactions and application to personalized medical care скачать в хорошем качестве

Interindividual differences in drug interactions and application to personalized medical care

Introduction of Research by Division of Clinical Pharmacy, Faculty of Pharmacy, Keio University Professor HIsakazu Ohtani Even after a new drug has been vetted in numerous clinical trials and approved for marketing, it is still far from a finished product. Pharmacy plays an important role in nurturing a new drug through the post-marketing phase, and this process can be just as important as drug discovery. The Division of Clinical Pharmacy in the Faculty of Pharmacy at Keio University is primarily involved in studying drugs after they have been marketed. We identify clinically relevant issues and conduct research to ensure the appropriate and effective use of drugs. "Before a drug reaches the market, most manufacturers will be focused on investigating whether a drug really works as promised. Once a drug is launched, this can present a problem. Companies do conduct many clinical trials to check for adverse drug reactions and significant drug interactions, but the drug is only tested in a limited number of people before it is sold, so reliable information on adverse drug reactions and drug interactions needs bolstering. Of particular concern is the availability of data on adverse drug reactions and other drug-related information that could impact patient safety. Studying adverse drug reactions and drug interactions in patients or healthy volunteers presents ethical issues since potential harm may be involved. The practical approach is to conduct laboratory research, using such as animals or enzymes or computer simulations, instead of people. These are becoming our primary forms of research." Sometimes, the cause of the adverse reaction cannot be identified. But in many cases, the fault lies in human error, such as inadequate monitoring of drug therapy, or overdose, and these issues can be solved by improving drug usage practices. One of these is exercising caution when combining two or more drugs. "Drug interactions can occur through various mechanisms. Ruling out just one mode is not effective, but one of the most common causes is inhibition of drug metabolizing enzymes. To elaborate, our bodies produce enzymes that metabolize drugs (biotransformation). If you’ve had a drink, an enzyme (alcohol dehydrogenase) will break down the alcohol and detoxify it so that blood alcohol levels decrease over time. Drugs are metabolized by enzymes that break down drugs and eliminate them from the body. Imagine we have a drug called A. There is an enzyme that metabolizes Drug A. But if you happen to take Drug B with Drug A, it can inhibit the metabolic enzyme and prevent A from being detoxified. This is metabolic enzyme inhibition. It can cause a drug to have excessive effects, or may even cause an adverse drug reaction." Metabolic enzymes are made up of proteins, and genes provide the blueprints to create those proteins. A difference in genetic information will code for a protein with a slightly different amino acid sequence. Resulting enzymes have different structures and characteristics which may render the metabolic enzyme more (or less) susceptible to inhibition in that particular individual. This means that when two drugs or more are taken together, some people will have metabolic enzymes that may cause extremely potent drug effects (because the drug is not detoxified), while others with different genes will only experience mild drug effects. "If we could determine an individual's risk for drug interactions based on his genes, and know in advance that a major or minor adverse drug reaction might occur, we could avoid giving dangerous drug combinations to those at risk. Or at least administer the drugs very cautiously. The goal is to minimize patients' risk by determining who is at risk, and minimize adverse drug reactions or drug interactions to provide better pharmacotherapy. Ultimately, I believe this will improve patients' quality of life (QOL)." The Division of Clinical Pharmacy is open to future opportunities for international collaboration, and is currently in the process of accumulating information through a wide variety of experiments and computer simulations and provides this data to those involved in patient care and drug development. Our goal is to take our knowledge of patient predisposition, genotype, and other individual characteristics, and apply it in customizing pharmacotherapy, to provide better personalized medical care.