News

New Name and Additional Data! for the CYP/P-gp Substrates and Perpetrators Lists

Our new “DDI Marker Studies Knowledgebase” (in Excel) is now available in the Resource Center and replaces the previous combined and individual lists of CYP/P-gp substrates and perpetrators.

The Knowledgebase represents a comprehensive list of compounds that are sensitive or moderate sensitive substrates (NEW), inhibitors, or inducers of CYP enzymes (weak-to-strong potency assigned) and the P-gp transporter.

You can generate an individual list of a specific CYP isoform or transporter as shown in the video (at the bottom of the page).

Additionally, the Knowledgebase provides useful information on the compounds therapeutic class, clinical recommended dosage, pharmacokinetics (e.g., dose proportionality, accumulation ratio, time to steady-state), QT prolongation, and NTI characteristics.

The Knowledgebase will be updated quarterly.

Feel free to contact us if you experience any issues or if you have any questions or suggestions. Your feedback is always greatly valued!

Data Curation and Entry in DIDB – December Summary

In December, we added 89 citations in DIDB, including 37 in vitro (with 34 articles published in Dec. 2021) and 52 in vivo articles (with 30 articles published in Dec. 2021).

Five approved NDAs/BLAs were also added with the 4 following NDAs: asciminib (SCEMBLIX), avacopan (TAVNEOS), maralixibat (LIVMARLI), pafolacianine (CYTALUX), and 1 BLA: ropeginterferon alfa-2b (BESREMI)

You can check the citations that are recently published and entered in DIDB and all the NDAs/BLAs in DIDB.

As always, feel free to contact us if you have any questions or comments.

UW Pharmacy’s Drug Interaction Database, built to promote medication safety, wins national innovation award

2022 marks 20 years of DIDB licensing and the selection by the ASCPT of Dr. René Levy and Dr. Isabelle Ragueneau-Majlessi to receive the 2022 Gary Neil Prize for Innovation in Drug Development.

Read the story here: https://www.washington.edu/news/2022/01/13/uw-pharmacys-drug-interaction-database-built-to-promote-medication-safety-wins-national-innovation-award/

Exploring the Relationship of Drug BCS Classification, Food Effect, and Gastric pH-Dependent Drug Interactions

Abstract

Food effect (FE) and gastric pH-dependent drug-drug interactions (DDIs) are both absorption-related. Here, we evaluated if Biopharmaceutics Classification System (BCS) classes may be correlated with FE or pH-dependent DDIs. Trends in FE data were investigated for 170 drugs with clinical FE studies from the literature and new drugs approved from 2013 to 2019 by US Food and Drug Administration. A subset of 38 drugs was also evaluated to determine whether FE results can inform the need for a gastric pH-dependent DDI study. The results of FE studies were defined as no effect (AUC ratio 0.80-1.25), increased exposure (AUC ratio ≥1.25), or decreased exposure (AUC ratio ≤0.8). Drugs with significantly increased exposure FE (AUC ratio ≥2.0; N=14) were BCS Class 2 or 4, while drugs with significantly decreased exposure FE (AUC ratio ≤0.5; N=2) were BCS Class 1/3 or 3. The lack of FE was aligned with the lack of a pH-dependent DDI for all 7 BCS Class 1 or 3 drugs as expected. For the 13 BCS Class 2 or 4 weak base drugs with an increased exposure FE, 6 had a pH-dependent DDI (AUC ratio ≤0.8). Among the 16 BCS Class 2 or 4 weak base drugs with no FE, 6 had a pH-dependent DDI (AUC ratio ≤0.8). FE appears to have limited correlation with BCS classes except for BCS Class 1 drugs, confirming that multiple physiological mechanisms can impact FE. Lack of FE does not indicate absence of pH-dependent DDI for BCS Class 2 or 4 drugs.

Data Curation and Entry in DIDB – November Summary

In November, we added 142 citations in DIDB, including 41 in vitro (with 25 articles published in Nov 2021) and 101 in vivo articles (with 40 articles published in Nov 2021).

Five approved NDAs/BLA were also added, with the 3 following NDAs: atogepant (QULIPTA), difelikefalin (KORSUVA), mobocertinib (EXKIVITY), and 2 BLAs: lonapegsomatropin (SKYTROFA), tisotumab vedotin (TIVDAK)

You can check the citations that are recently published and entered in DIDB and all the NDAs/BLAs in DIDB.

As always, feel free to contact us if you have any questions or comments.

Evaluating the feasibility of performing pharmacogenetic guided-medication therapy management in a retirement community: A prospective, single arm study

J Am Coll Clin Pharm. 2021;1-11
  • doi: 10.1002/jac5.1570
  • Semantic Scholar
  • Abstract

    New drug application reviews contain critical drug interaction study results with newly approved drugs tested both as victims and as perpetrators of drug-drug interactions (DDIs). Pharmacokinetic-based DDI data for drugs approved by the US Food and Drug Administration in 2013–2017 (N = 137) were analyzed using the University of Washington Drug Interaction Database. For the largest metabolism- and transporter-based drug interactions, defined as a change in exposure ≥ 5-fold in victim drugs, the mechanisms and clinical relevance were characterized. Consistent with the major role of CYP3A in drug disposition, CYP3A inhibition and induction explained a majority of the observed interactions (new drugs as victims or as perpetrators). However, transporter-mediated interactions were also prevalent, with OATP1B1/1B3 playing a significant role. As victims, 17 and 4 new molecular entities (NMEs) were identified to be sensitive substrates of enzymes and transporters, respectively. When considered as perpetrators, three drugs showed strong inhibition of CYP3A, one was a strong CYP3A inducer, and two showed strong inhibition of transporters (OATP1B1/1B3 and/or BCRP). All DDIs with AUC changes ≥ 5-fold had labeling recommendations in their respective drug labels, contraindicating or limiting the coadministration with known substrates or perpetrators of the enzyme/transporter involved. The majority of sensitive substrates or strong inhibitors were oncology and antiviral treatments, suggesting a significant risk of DDIs in these patient populations for whom therapeutic management is already complex due to poly-therapy. Pharmacogenetic studies and physiologically based pharmacokinetic models were commonly used to assess the drug interaction potential in specific populations and clinical scenarios. Finally, absorption-based DDIs were evaluated in approximately 30% of drug applications, and 14 NMEs had label recommendations based on the results.

    Data Curation and Entry in DIDB – October Summary

    In October, we added 149 citations in DIDB, including 50 in vitro (with 14 articles published in Oct 2021) and 99 in vivo articles (with 35 articles published in Oct 2021).

    Five recently approved NDAs/BLAs were also added with the 4 following NDAs: belumosodil (REZUROCK), belzutifan (WELIREG), fexinidazole (FEXINIDAZOLE TABLETS), and odevixibat (BYLVAY), and 1 BLA: anifrolumab (SAPHNELO)

    You can check the citations that are recently published and entered in DIDB and all the NDAs/BLAs in DIDB.

    As always, feel free to contact us if you have any questions or comments.

    New features! and improvement of existing queries

    DIDB has been updated with the following new features:

    • Citations recently published” and “NDA/BLAs recently enters” can retrieve citations and NDA/BLAs containing PGx data only
    • The above result pages show if the citation or NDA/BLA contains in vitroin vivo, or PGx content
    • All the “In Vitro Parameter Queries” take multiple compounds
    • All query results now 
      • use the therapeutic class format of presenting two levels, e.g., “Antiemetics ⟶ Neurokinin-1 Receptor Antagonist”
      • both levels of the therapeutic class are links directed to the therapeutic class DDI risk assessment
      • drug names are now links if there is any DDI summary/QT summary/PK profile in their monographs

    Feel free to contact us if you experience any issues or if you have any questions or suggestions. Your feedback is always greatly valued!

    Lists of Sensitive Substrates, Inhibitors and Inducers updated

    The lists of sensitive substrates, inhibitors, and inducers, including the file combining all lists, have been updated and are available in the DIDB Resource Center.

    A total of 18 drug interactions, involving 13 drugs, were added to the October version or were updated. Nine of these drugs were cancer treatments, including 7 kinase inhibitors, being identified as sensitive substrates or perpetrators of CYP enzymes or the P-gp transporter.

    As always, feel free to contact us if you have any questions or comments.

    Data Curation and Entry in DIDB – September Summary

    In September, we added 118 citations in DIDB, including 56 in vitro (with 29 articles published in Sept. 2021) and 62 in vivo articles (with 35 articles published in Sept. 2021).

    Four recently approved NDAs/BLAs were also added with the 2 following NDAs: ibrexafungerp (BREXAFEMME) and viloxazine (QELBREE) and 2 following BLAs: asparaginase erwinia (RYLAZE) and avalglucosidase alfa (NEXVIAZYME).

    You can check the citations that are recently published and entered in DIDB and all the NDAs/BLAs in DIDB.

    As always, feel free to contact us if you have any questions or comments.