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Does In Vitro Potency Predict Clinically Efficacious Concentrations?

Jansson-Lofmark, Rasmus and Hjorth, Stephan and Gabrielsson, Johan (2020). Does In Vitro Potency Predict Clinically Efficacious Concentrations? Clinical Pharmacology and Therapeutics. 108 , 298-305
[Research article]

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The in vitro affinity of a compound for its target is an important feature in drug discovery, but what remains is how predictive in vitro properties are of in vivo therapeutic drug exposure. We assessed the relationship between in vitro potency and clinically efficacious concentrations for marketed small molecule drugs (n = 164) and how they may differ depending on therapeutic indication, mode of action, receptor type, target localization, and function. Approximately 70% of compounds had a therapeutic unbound plasma exposure lower than in vitro potency; the median ratio of exposure in relation to in vitro potency was 0.32, and 80% had ratios within the range of 0.007 to 8.7. We identified differences in the in vivo-to-in vitro potency ratio between indications, mode of action, target type, and matrix localization, and whether or not the drugs had active metabolites. The in vitro-assay variability contributions appeared to be the smallest; within the same drug target and mode of action the within-variability was slightly broader; but both were substantially less compared with the overall distribution of ratios. These data suggest that in vitro potency conditions, estimated in vivo potency, required level of receptor occupancy, and target turnover are key components for further understanding the link between clinical drug exposure and in vitro potency.

Authors/Creators:Jansson-Lofmark, Rasmus and Hjorth, Stephan and Gabrielsson, Johan
Title:Does In Vitro Potency Predict Clinically Efficacious Concentrations?
Series Name/Journal:Clinical Pharmacology and Therapeutics
Year of publishing :2020
Page range:298-305
Number of Pages:8
Publisher:Wiley Periodicals, Inc., American Society for Clinical Pharmacology and Therapeutics
Publication Type:Research article
Article category:Scientific peer reviewed
Version:Published version
Copyright:Creative Commons: Attribution-Noncommercial 4.0
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 3 Medical and Health Sciences > 301 Basic Medicine > Pharmacology and Toxicology
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Additional ID:
Type of IDID
Web of Science (WoS)000531160000001
ID Code:17389
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Department of Biomedical Science and Veterinary Public Health
Deposited By: SLUpub Connector
Deposited On:02 Sep 2020 09:59
Metadata Last Modified:15 Jan 2021 19:22

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