For more than 20 years, the University of Washington has been home to a database built, maintained and expanded around the goal of helping to prevent health complications from adverse drug reactions, one of the leading causes of injury and death in health care settings.
This year, the UW School of Pharmacy’s Drug Interaction Database, or DIDB — the core research tool in the school’s nonprofit Drug Interaction Solutions organization — is celebrating both a national award for innovation and its independent funding since 2002 through licensing agreements with companies, research institutes and regulatory agencies around the globe.
“The award from the American Society for Clinical Pharmacology & Therapeutics is a great acknowledgement of the impact we’ve had in the drug development space,” said Dr. Isabelle Ragueneau-Majlessi, DIDB co-founder and director of Drug Interaction Solutions. “We built something from scratch at the University of Washington, and now it is internationally recognized as an authoritative research tool, with over 180 organizations from 40 different countries as subscribers.”
The Drug Interaction Database is a highly detailed, structured matrix of cross-linking entries designed to support research and regulatory scientists in academia, pharmaceutical companies and other organizations in their evaluation of drug interactions and drug safety. Entries for the database are curated by UW scientists from a wide range of drug-related documents, including clinical studies, drug developer publications, toxicity case reports and FDA New Drug Applications reviews.
The database is continuously updated as new information about drugs becomes available. Currently, the site has more than 170,000 entries involving in vitro (or “test-tube experiments”) and in vivo (in humans) data on metabolic enzymes and drug transporters (proteins in the body that help drugs pass from one organ to another); interactions with other drugs or with foods, herbs, tobacco and genetics; and other factors.
The Drug Interaction Solutions team of experts not only thoroughly reviews drug interaction information but also helps researchers use the system effectively.
“The impetus to initiate this database resulted from my work with antiepileptic drugs. My eureka moment occurred in 1994 when I became able to segregate the clinical interactions of the drug phenytoin (Dilantin) according to two distinct but related enzymes. That ‘discovery’ propelled my efforts to pursue the development of the database,” said René Levy, the founder of the DIDB and its principal investigator until 2009, when he retired from the UW. Levy has widely published in the field of drug disposition and drug-to-drug interactions and remains an advisor to the director.
“This award recognizes the excellence and dedication of the team of database researchers, as well as the input I received from colleagues in the departments of Pharmaceutics and Medicinal Chemistry in the School of Pharmacy, and the Department of Neurological Surgery in the School of Medicine,” Levy said.
After establishing the plan for building the database and recruiting Ragueneau-Majlessi, Levy was able to gain funding initially through seed grants from several pharmaceutical companies. In 2002, the university began licensing access to the database through an arrangement with UW CoMotion. Since then, Drug Interaction Solutions has remained a nonprofit venture with licensing revenues used to cover the costs of scientific and technical maintenance, as well as the development of new features.
“The DIDB is a prime example of a university-sourced innovation maintained by the university and made available as products directly to customers, as opposed to licensed to others or spun off as a company,” said Roï Eisenkot, senior innovation manager at CoMotion. “As a longtime partner of the program, UW CoMotion has been collaborating with the team to build its licensing offerings and expand into new markets, while supporting all partner contracting activities such as risk management, managing distributors, fee collection and license renewals.”
While the database is not intended for doctors in clinical settings to use directly, Ragueneau-Majlessi explained, it is evolving in that direction through the integration of its data into the tools that help doctors make drug choices and manage adverse drug interactions.
According to the FDA, two-thirds of patient visits result in a prescription, with more drug combinations being used to treat patients. Adverse drug reactions “increase exponentially with four or more medications,” the agency writes. In addition, herbals and food products (including fruit juices) can significantly affect various common medications, so multi-drug interactions are frequent in clinical situations.
“It should not be acceptable that a person can be given two drugs with a major adverse interaction when we know the mechanism behind that interaction,” Ragueneau-Majlessi said. “We have the mechanistic and quantitative understanding that allow us to predict drug interactions, and that is very powerful clinically. Adverse drug interactions can be prevented.”
On its website, the Drug Interaction Solutions team states the DIDB can support the growth of personalized medicine and the trend toward selecting the most appropriate drug and dose for each unique patient.
“I really believe that is the next stage for the database,” Ragueneau-Majlessi said. “We are now in the era of precision dosing and personalized therapy. And, even if we can’t prevent all drug interactions, we can manage them. If you understand the mechanism of the drug and its interactions, you can make sure that an individual patient is not negatively affected. Knowledge is power.”
Levy and Ragueneau-Majlessi will officially receive the Gary Neil Prize for Innovation in Drug Development from the American Society for Clinical Pharmacology & Therapeutics in March at the society’s annual meeting. The award honors scientists in clinical pharmacology who “have demonstrated leadership in the application of significant, innovative science to clinical drug development.”
For more information contact Marie-Christine Bodinier, senior marketing manager for Drug Interaction Solutions, at [email protected]