Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Prediction and Classification of the Uptake and Disposition of Antidepressants and New CNS-Active Drugs in the Human Brain using the ANDROMEDA by Prosilico Software and Brainavailability-Matrix

View ORCID ProfileUrban Fagerholm, Sven Hellberg, View ORCID ProfileJonathan Alvarsson, View ORCID ProfileOla Spjuth
doi: https://doi.org/10.1101/2022.09.28.509936
Urban Fagerholm
1Prosilico AB, Lännavägen 7, SE-141 45 Huddinge, Sweden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Urban Fagerholm
  • For correspondence: urban.fagerholm@prosilico.com
Sven Hellberg
1Prosilico AB, Lännavägen 7, SE-141 45 Huddinge, Sweden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jonathan Alvarsson
2Department of Pharmaceutical Biosciences and Science for Life Laboratory, Uppsala University, Box 591, SE-751 24 Uppsala, Sweden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jonathan Alvarsson
Ola Spjuth
1Prosilico AB, Lännavägen 7, SE-141 45 Huddinge, Sweden
2Department of Pharmaceutical Biosciences and Science for Life Laboratory, Uppsala University, Box 591, SE-751 24 Uppsala, Sweden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Ola Spjuth
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

Background Passive blood-brain barrier permeability (BBB Pe), fraction bound to brain tissue (fb,brain) and efflux by transport proteins MDR-1 and BCRP are essential determinants for the brain uptake and disposition of drugs.

Methods The main objective of the study was to use the software ANDROMEDA by Prosilico to predict passive BBB Pe- and fb,brain-classes and MDR-1- and BCRP-specificities for various classes of antidepressants and for CNS-active small drugs marketed during 2020 and 2021, and then to position them according to a new 2-dimensional Brainavailability-Matrix (8 passive BBB Pe x 4 fb,brain classes, where class 11 has highest and 84 lowest values/brainavailability). Predicted estimates were used, except for cases where measured values were available.

Results and Conclusion Results for 53 drugs show that adequate CNS uptake and disposition are achieved for compounds placed in the zones for low, moderate and high brainavailability, despite efflux. They also show that high brainavailability and efflux are common for CNS-active drugs and that modern CNS-active drugs generally have lower brainavailability than older antidepressive drugs. Furthermore, they demonstrate that ANDROMEDA by Prosilico and the new Brainavailability-Matrix are applicable for prediction, optimization and positioning of CNS uptake and disposition of drugs and drug candidates in man.

Competing Interest Statement

Urban Fagerholm, Ola Spjuth and Sven Hellberg declare shares in Prosilico AB, a Swedish company that develops solutions for human clinical ADME/PK predictions.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
Back to top
PreviousNext
Posted September 30, 2022.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Prediction and Classification of the Uptake and Disposition of Antidepressants and New CNS-Active Drugs in the Human Brain using the ANDROMEDA by Prosilico Software and Brainavailability-Matrix
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Prediction and Classification of the Uptake and Disposition of Antidepressants and New CNS-Active Drugs in the Human Brain using the ANDROMEDA by Prosilico Software and Brainavailability-Matrix
Urban Fagerholm, Sven Hellberg, Jonathan Alvarsson, Ola Spjuth
bioRxiv 2022.09.28.509936; doi: https://doi.org/10.1101/2022.09.28.509936
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Prediction and Classification of the Uptake and Disposition of Antidepressants and New CNS-Active Drugs in the Human Brain using the ANDROMEDA by Prosilico Software and Brainavailability-Matrix
Urban Fagerholm, Sven Hellberg, Jonathan Alvarsson, Ola Spjuth
bioRxiv 2022.09.28.509936; doi: https://doi.org/10.1101/2022.09.28.509936

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Pharmacology and Toxicology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4397)
  • Biochemistry (9621)
  • Bioengineering (7117)
  • Bioinformatics (24925)
  • Biophysics (12649)
  • Cancer Biology (9984)
  • Cell Biology (14390)
  • Clinical Trials (138)
  • Developmental Biology (7982)
  • Ecology (12141)
  • Epidemiology (2067)
  • Evolutionary Biology (16018)
  • Genetics (10945)
  • Genomics (14771)
  • Immunology (9895)
  • Microbiology (23723)
  • Molecular Biology (9500)
  • Neuroscience (51032)
  • Paleontology (370)
  • Pathology (1544)
  • Pharmacology and Toxicology (2689)
  • Physiology (4034)
  • Plant Biology (8687)
  • Scientific Communication and Education (1512)
  • Synthetic Biology (2403)
  • Systems Biology (6452)
  • Zoology (1349)