The DIDB team will be exhibiting at the 17th International Conference on Drug-Drug Interactions in Seattle on June 30-July 2, 2014, and will contribute to the scientific program with two presentations:
* Critical Review of the 2013-2014 Literature (Dr. Sophie Argon)
* New Molecular Entities Approved by FDA in 2013: Review of In Vitro and In Vivo Data (Dr. Jingjing Yu)
Dr. Ragueneau-Majlessi will be chairing the session entitled “NDA and Literature Update” on June 30th.
The DIDB program is pleased to announce the release of e-PKGene Version 2.0.
Please see this detailed description of the new features.
New features include:
Check out the new DIDB at https://didb.druginteractionsolutions.org
If a picture is worth a thousand words, a fully functioning website is worth a thousand pictures. Check it out https://didb.druginteractionsolutions.org.
This new version of DIDB went live on November 3rd.
If you have any questions or comments please contact us.
Please visit the DIDB Team at Booth #602 during this year’s 10th International ISSX Meeting to be held in Toronto, Canada September 29 – October 3, 2013.
Also, please come to the following poster presentation:
Dr. Nina Isoherannen, Associate Professor in Pharmaceutics, will become a part-time scientific contributor for the Drug Interaction Database program as of July 1st, 2013.
The DIDB platform will be upgraded this week-end to run with the latest version of its software. If you experience any issue, please contact us.
A new gene summary for CYP3A4 gene polymorphism is available in the Summaries section of e-PKGene. As usual, comments and suggestions are welcome!
The DIDB program has released its pharmacogenetic database, e-PKGene. For more information on e-PKgene please see the e-PKGene User Guide.
Part of the release also includes a new website where DIDB users can easily access both applications with a single login.
First, you need to register and create an individual account. To do so, use your current company login/password for the DIDB, and follow the few steps. When asked to provide your email address, please provide your WORK email.
If you have any questions regarding the release or experience any difficulty creating your new password, please contact us.
Drugs that are mainly cleared by a single enzyme are considered more sensitive to drug-drug interactions (DDIs) than drugs cleared by multiple pathways. However, whether this is true when a drug cleared by multiple pathways is coadministered with an inhibitor of multiple P450 enzymes (multi-P450 inhibition) is not known. Mathematically, simultaneous equipotent inhibition of two elimination pathways that each contribute half of the drug clearance is equal to equipotent inhibition of a single pathway that clears the drug. However, simultaneous strong or moderate inhibition of two pathways by a single inhibitor is perceived as an unlikely scenario. The aim of this study was (i) to identify P450 inhibitors currently in clinical use that can inhibit more than one clearance pathway of an object drug in vivo and (ii) to evaluate the magnitude and predictability of DDIs caused by these multi-P450 inhibitors. Multi-P450 inhibitors were identified using the Metabolism and Transport Drug Interaction Database. A total of 38 multi-P450 inhibitors, defined as inhibitors that increased the AUC or decreased the clearance of probes of two or more P450s, were identified. Seventeen (45%) multi-P450 inhibitors were strong inhibitors of at least one P450, and an additional 12 (32%) were moderate inhibitors of one or more P450s. Only one inhibitor (fluvoxamine) was a strong inhibitor of more than one enzyme. Fifteen of the multi-P450 inhibitors also inhibit drug transporters in vivo, but such data are lacking on many of the inhibitors. Inhibition of multiple P450 enzymes by a single inhibitor resulted in significant (>2-fold) clinical DDIs with drugs that are cleared by multiple pathways such as imipramine and diazepam, while strong P450 inhibitors resulted in only weak DDIs with these object drugs. The magnitude of the DDIs between multi-P450 inhibitors and diazepam, imipramine, and omeprazole could be predicted using in vitro data with similar accuracy as probe substrate studies with the same inhibitors. The results of this study suggest that inhibition of multiple clearance pathways in vivo is clinically relevant, and the risk of DDIs with object drugs may be best evaluated in studies using multi-P450 inhibitors.
e-PKGene (www.pharmacogeneticsinfo.org) is a manually curated knowledge product developed in the Department of Pharmaceutics at the University of Washington, USA. The tool integrates information from the literature, public repositories, reference textbooks, product prescribing labels and clinical review sections of new drug approval packages. The database’s easy-to-use web portal offers tools for visualisation, reporting and filtering of information. The database helps scientists to mine pharmacokinetic and pharmacodynamic information for drug-metabolising enzymes and transporters, and provides access to available quantitative information on drug exposure contained in the literature. It allows in-depth analysis of the impact of genetic variants of enzymes and transporters on pharmacokinetic responses to drugs and metabolites. This review gives a brief description of the database organisation, its search functionalities and examples of use.