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 …
Hepatic clearance concepts and misconceptions: Why the well-stirred model is still used even though it is not physiologic reality?
The liver is the most important drug metabolizing organ, endowed with a plethora of
metabolizing enzymes and transporters to facilitate drug entry and removal via metabolism …
metabolizing enzymes and transporters to facilitate drug entry and removal via metabolism …
Advancing Predictions of Tissue and Intracellular Drug Concentrations Using In Vitro, Imaging and Physiologically Based Pharmacokinetic Modeling Approaches
Y Guo, X Chu, NJ Parrott, KLR Brouwer… - Clinical …, 2018 - Wiley Online Library
This white paper examines recent progress, applications, and challenges in predicting
unbound and total tissue and intra/subcellular drug concentrations using in vitro and …
unbound and total tissue and intra/subcellular drug concentrations using in vitro and …
Extrapolation of in vivo hepatic clearance from in vitro uptake clearance by suspended human hepatocytes for anionic drugs with high binding to human albumin …
SJ Kim, KR Lee, S Miyauchi, Y Sugiyama - Drug Metabolism and …, 2019 - ASPET
We investigated whether human serum albumin (HSA) in suspended human hepatocytes
would affect the uptake clearance of anionic drugs with high binding to HSA and improve the …
would affect the uptake clearance of anionic drugs with high binding to HSA and improve the …
Quantitative contribution of six major transporters to the hepatic uptake of drugs:“SLC-phenotyping” using primary human hepatocytes
Y Bi, C Costales, S Mathialagan, M West… - … of Pharmacology and …, 2019 - ASPET
Hepatic uptake transporters [solute carriers (SLCs)], including organic anion transporting
polypeptide (OATP) 1B1, OATP1B3, OATP2B1, sodium-dependent taurocholate …
polypeptide (OATP) 1B1, OATP1B3, OATP2B1, sodium-dependent taurocholate …
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 …
Preincubation Time-Dependent, Long-Lasting Inhibition of Drug Transporters and Impact on the Prediction of Drug− Drug Interactions
Y Nozaki, S Izumi - Drug Metabolism and Disposition, 2023 - ASPET
Transporter-mediated drug− drug interaction (DDI) is of clinical concern, and the quantitative
prediction of DDIs is an indispensable part of drug development. Cell-based inhibition …
prediction of DDIs is an indispensable part of drug development. Cell-based inhibition …
Recent developments in in vitro and in vivo models for improved translation of preclinical pharmacokinetics and pharmacodynamics data
J Yadav, M El Hassani, J Sodhi… - Drug metabolism …, 2021 - Taylor & Francis
Improved pharmacokinetics/pharmacodynamics (PK/PD) prediction in the early stages of
drug development is essential to inform lead optimization strategies and reduce attrition …
drug development is essential to inform lead optimization strategies and reduce attrition …
Role of Hepatic Organic Anion Transporter 2 in the Pharmacokinetics of R- and S-Warfarin: In Vitro Studies and Mechanistic Evaluation
Y Bi, J Lin, S Mathialagan, L Tylaska… - Molecular …, 2018 - ACS Publications
Interindividual variability in warfarin dose requirement demands personalized medicine
approaches to balance its therapeutic benefits (anticoagulation) and bleeding risk …
approaches to balance its therapeutic benefits (anticoagulation) and bleeding risk …
A complete extension of classical hepatic clearance models using fractional distribution parameter fd in physiologically based pharmacokinetics
YS Jeong, WJ Jusko - Journal of Pharmaceutical Sciences, 2024 - Elsevier
The classical organ clearance models have been proposed to relate the plasma clearance
CL p to probable mechanism (s) of hepatic clearance. However, the classical models …
CL p to probable mechanism (s) of hepatic clearance. However, the classical models …