We have changed our domain to match our new name of UW Drug Interaction Solutions. We feel this name change better reflects our expanding activities and offerings.
All old bookmarks and links will still work, they will be redirected to the same page on our new domain.
If you have any questions or issues please contact us.
As always, don’t forget to check us out and follow us on Linked.
New queries are now available for beta testing under “FDA Marker Queries”. They allow you to search for in vitro and clinical data for inhibitors of CYP markers, and, in a second step from the query results page, view clinical concentrations of each inhibitor.
We are looking forward to your feedback!
As the research into the organic anion transporting polypeptides (OATPs) continues to grow, it is important to ensure that the data generated are accurate and reproducible. In the in vitro evaluation of OATP1B1/1B3 inhibition, there are many variables that can contribute to variability in the resulting inhibition constants, which can then, in turn, contribute to variable results when clinical predictions (R-values) are performed. Currently, the only experimental condition recommended by the US Food and Drug Administration (FDA) is the inclusion of a pre-incubation period.1 To identify other potential sources of variability, a descriptive analysis of available in vitro inhibition data was completed. For each of the 21 substrate/inhibitor pairs evaluated, cell type and pre-incubation were found to have the greatest effect on half-maximal inhibitory concentration (IC50 ) variability. Indeed, when only HEK293 cells and co-incubation conditions were included, the observed variability for the entire data set (highest IC50 /lowest) was reduced from 12.4 to 5.2. The choice of probe substrate used in the study also had a significant effect on inhibitor constant variability. Interestingly, despite the broad range of inhibitory constants identified, these two factors showed little effect on the calculated R-values relative to the FDA evaluation cutoff of 1.1 triggering a clinical evaluation for the inhibitors evaluated. However, because of the small data set available, further research is needed to confirm these preliminary results and define best practice for the study of OATPs.
The posters presented at the 12th International ISSX Meeting in Portland by the DIDB team are now available in the Resource Center’s DIDB Team’s Most Recent Communications section:
Presented at ISSX conference, June 2019, Portland, OR, USA
Savannah J. McFeely, Yu, Tasha K. Ritchie, and Isabelle Ragueneau-Majlessi
The effect of inhibition of the organic anion transporting polypeptides (OATP) 1B1 and 1B3 has continued to grow in clinical significance and recognition. In the last five years, a signification portion of newly approved drugs in the US have been shown to be inhibitors of OATP1B1 and/or OATP1B3 in vitro. For this reason, it is critical to understand the effect of experimental variability on drug interaction predictions and how it impacts the decision for a clinical evaluation.
Presented at ISSX conference, June 2019, Portland, OR, USA
Jingjing Yu, Ichiko Petrie, and Isabelle Ragueneau-Majlessi
The aim of the present work was to review pharmacokinetic drug-drug interaction (DDI) data available in New Drug Applications (NDAs) for drugs approved by the US Food and Drug Administration in 2018 and analyze the mechanisms mediating interactions that triggered label recommendations.
We will be updating the homepage and the public content of our website over the coming few weeks, with an early version released next week. Our new program name, UW Drug Interaction Solutions, reflects our expanding activities and offerings. You can view/download a new brochure and technical flyers on our redesigned homepage.
Note that once you have logged in, the web pages dedicated to subscribers have not changed and you will find all the queries, functions, and editorial content you are used to.
We have also launched a LinkedIn page for UW Drug Interaction Solutions where you can find the most recent news and events regarding the program.
The UW Drug Interaction Database team will be attending the 12th International ISSX Meeting in Portland next week. In addition to our booth #316, we hope to meet you at one of our posters:
Drs. Jingjing Yu, Sophie Argon, and Savannah McFeely will speak at the upcoming 22nd International Conference on Drug-Drug Interactions, June 20-22, Seattle WA.
Also, visit our exhibit booth during the conference to learn about new developments and upcoming features.
The importance of uptake transporters in determining drug disposition is increasingly appreciated. While the focus of regulatory agencies worldwide has been on the hepatic organic anion transporting polypeptides (OATPs)-1B1 and-1B3, there is another isoform of the OATP sub-family, OATP2B1, which should be considered equally relevant. Unlike the other members of the OATP sub-family, OATP2B1 is expressed in multiple organs in humans, including in the intestine and the liver. Similar to other OATPs, OATP2B1 mediates the hepatic and intestinal uptake of many drugs and endogenous compounds. The importance of OATP2B1 in the disposition of many drugs is highlighted by the growing recognition of its role in significant in vivo drug-drug or food-drug interactions. The dramatic changes in drug exposure attributable to inhibition of OATP2B1 highlight the importance of developing a better understanding of the clinical role of OATP2B1. This review aims to provide a thorough summary of the current understanding of the pharmacogenetics, regulation, expression and abundance of OATP2B1 in humans, as well as its clinical relevance in drug-drug and food-drug interactions.