The next frontier in ADME science: Predicting transporter-based drug disposition, tissue concentrations and drug-drug interactions in humans
Predicting transporter-based drug clearance (CL) and tissue concentrations (TC) in humans
is important to reduce the risk of failure during drug development. In addition, when …
is important to reduce the risk of failure during drug development. In addition, when …
Drug concentration asymmetry in tissues and plasma for small molecule–related therapeutic modalities
The well accepted “free drug hypothesis” for small-molecule drugs assumes that only the
free (unbound) drug concentration at the therapeutic target can elicit a pharmacologic effect …
free (unbound) drug concentration at the therapeutic target can elicit a pharmacologic effect …
Toward a consensus on applying quantitative liquid chromatography‐tandem mass spectrometry proteomics in translational pharmacology research: a white paper
Quantitative translation of information on drug absorption, disposition, receptor engagement,
and drug–drug interactions from bench to bedside requires models informed by …
and drug–drug interactions from bench to bedside requires models informed by …
In vitro and in vivo methods to assess pharmacokinetic drug– drug interactions in drug discovery and development
C Lu, L Di - Biopharmaceutics & drug disposition, 2020 - Wiley Online Library
Drug–drug interactions (DDIs) caused by the co‐administration of multiple drugs are major
safety concerns in the clinic. Several drugs have been withdrawn from the market due to …
safety concerns in the clinic. Several drugs have been withdrawn from the market due to …
Successful and unsuccessful prediction of human hepatic clearance for lead optimization
Development of new chemical entities is costly, time-consuming, and has a low success
rate. Accurate prediction of pharmacokinetic properties is critical to progress compounds …
rate. Accurate prediction of pharmacokinetic properties is critical to progress compounds …
Plasma protein-mediated uptake and contradictions to the free drug hypothesis: a critical review
JA Schulz, DM Stresser, JC Kalvass - Drug metabolism reviews, 2023 - Taylor & Francis
According to the free drug hypothesis (FDH), only free, unbound drug is available to interact
with biological targets. This hypothesis is the fundamental principle that continues to explain …
with biological targets. This hypothesis is the fundamental principle that continues to explain …
Application of empirical scalars to enable early prediction of human hepatic clearance using in vitro-in vivo extrapolation in drug discovery: an evaluation of 173 drugs
RS Jones, C Leung, JH Chang, S Brown, N Liu… - Drug Metabolism and …, 2022 - ASPET
The utilization of in vitro data to predict drug pharmacokinetics (PK) in vivo has been a
consistent practice in early drug discovery for decades. However, its success is hampered …
consistent practice in early drug discovery for decades. However, its success is hampered …
Primary human hepatocyte spheroids as an in vitro tool for investigating drug compounds with low hepatic clearance
J Riede, BM Wollmann, E Molden… - Drug Metabolism and …, 2021 - ASPET
Characterizing the pharmacokinetic properties of drug candidates represents an essential
task during drug development. In the past, liver microsomes and primary suspended …
task during drug development. In the past, liver microsomes and primary suspended …
Impact of plasma protein binding in drug clearance prediction: a database analysis of published studies and implications for in vitro-in vivo extrapolation
LJ Francis, JB Houston, D Hallifax - Drug Metabolism and Disposition, 2021 - ASPET
Plasma protein–mediated uptake (PMU) and its effect on clearance (CL) prediction have
been studied in various formats; however, a comprehensive analysis of the overall impact of …
been studied in various formats; however, a comprehensive analysis of the overall impact of …
Investigating the Theoretical Basis for In Vitro–In Vivo Extrapolation (IVIVE) in Predicting Drug Metabolic Clearance and Proposing Future Experimental Pathways
Extensive studies have been conducted to predict in vivo metabolic clearance from in vitro
human liver metabolism parameters (ie, in vitro–in vivo extrapolation (IVIVE)) with little …
human liver metabolism parameters (ie, in vitro–in vivo extrapolation (IVIVE)) with little …