The June Newsletter is now available. You can see this and past newsletters (published in 2020 and 2021) in the DIDB Resource Center. This is our last issue as you can now access the latest citations using our new citations search on the DIDB Home page. Please note that you must be signed in to access.
Do not hesitate to contact us with comments or suggestions.
We have initiated a [How to]… Series of 2-min videos, to show how to search, explore, use, some specific content in DIDB. So far, we have recorded videos on combination drugs, racemate and enantiomers, QT interval prolongation, and drug monographs.
If you have in mind any information you find difficult to retrieve in DIDB, feel free to let us know at email@example.com. We will get back to you and can decide to explain it in a short video.
The videos are available in DIDB Resource Center. Please note that you must be signed in to access.
Senior team members, Dr Jingjing Yu and Dr Cathy Yeung, are instructing a CE course on Principles & Mechanisms of Pharmacokinetic Drug-Drug Interactions for Recently Approved Drugs which provides pharmaceutical scientists and clinical pharmacists with an in-depth understanding of the mechanisms of drug interactions.
This 5-session course was prepared in collaboration with University of Wisconsin-Madison.
To learn more and register, visit here.
The lists of sensitive substrates, inhibitors, and inducers, including the file combining all lists, have been updated and are available in the Resource Center.
As always, feel free to contact us if you have any questions or comments.
Clin Pharmacol Ther.
Published online 2021 Apr 09
Evaluating the potential of new drugs and their metabolites to cause drug‐drug interactions (DDIs) is critical for understanding drug safety and efficacy. Although multiple analyses of proprietary metabolite testing data have been published, no systematic analyses of metabolite data collected according to current testing criteria have been conducted. To address this knowledge gap, 120 new molecular entities approved between 2013 and 2018 were reviewed. Comprehensive data on metabolite‐to‐parent area‐under‐the‐curve ratios (AUCM/AUCP), inhibitory potency of parent and metabolites, and clinical drug‐drug interactions (DDI) were collected. 64% of the metabolites quantified in vivo had AUCM/AUCP≥25% and 75% of these metabolites were tested for cytochrome P450 (CYP) inhibition in vitro, resulting in 15 metabolites with potential DDI risk identification. While 50% of the metabolites with AUCM/AUCP<25% were also tested in vitro, none of them showed meaningful CYP inhibition potential. The metabolite % plasma total radioactivity cutoff of ≥10% did not appear to add value to metabolite testing strategies. No relationship between metabolite versus parent drug polarity and inhibition potency was observed. Comparison of metabolite and parent maximum concentration (Cmax) divided by inhibition constant Ki values suggested that metabolites can contribute to in vivo DDIs and hence, quantitative prediction of clinical DDI magnitude may require both parent and metabolite data. This systematic analysis of metabolite data for newly approved drugs supports an AUCM/AUCP cutoff of ≥25% to warrant metabolite in vitro CYP screening to adequately characterize metabolite inhibitory DDI potential and support quantitative DDI predictions.
Presented virtually at ASCPT Annual Meeting, March 2021
2021 ASCPT Poster Presentation – Drug BCS classification and absorption-based DDIs
Katie Owens, Sophie Argon, Jingjing Yu, Isabelle Ragueneau-Majlessi, and colleagues at FDA
Food-effect (FE) and gastric pH-mediated drug-drug interactions (DDIs) are absorption-related. Here. we evaluated of the Biopharmaceutical Classification System (BCS) may be correlated with FE or pH-mediated DDI observed.
Presented virtually at ASCPT Annual Meeting, March 2021
2021 ASCPT Poster Presentation – DDI labeling language and clinical recommendations, digoxin as an example
Lindsay M. Henderson, Claire Steinbronn, Jingjing Yu, Cathy Yeung, and Isabelle Ragueneau-Majlessi
This study’s objective was to evaluate the consistency in DDI labeling language of recently marketed drugs (2012-2020) when found to alter the exposure of coadministered digoxin, a clinical P-glycoprotein (P-gp) substrate and narrow therapeutic index (NTI) medication.
We have recorded a one-hour long video tutorial suitable as a refresher training or to kick-start the use of DIDB. It starts by introducing the different lists available in the Resource Center of DIDB and then, it shows how to retrieve the human in vitro metabolism and transport information using preformulated queries. Finally it presents the in vivo datasets and how to retrieve clinical PK-based information from drug-drug interaction, food-effect, organ impairment and pharmacogenetics studies.
The video is available in DIDB Resource Center. Please note that you must be signed in to access.
We are pleased to provide access to an innovative online tool: DDPred, developed by the University of Lyon, France, that uses an in vivo static mechanistic model to predict PK-based DDIs with hundreds of substrates and inhibitors/inducers and evaluates the impact of polymorphism.
The link to this application will be available to all DIDB users during a 6-month evaluation. Please take the time to test it and to provide your feedback in the online survey. We value your feedback! Thank you.
DIDB has been updated with the following new features:
- Drug characteristics, e.g., substrate sensitivity, precipitant inhibition/induction potency, NTR, QT interval prolongation potential, are added into the drug monograph
- A list of drugs with identified drug characteristics are presented in the Resource Center
- “Advanced table search” function is added to filter the query results (in table view). See our updated video tutorial.
Feel free to contact us if you experience any issues or if you have any questions or suggestions. Your feedback is always greatly valued!