scholarly journals Revisiting a physiologically based pharmacokinetic model for cocaine with a forensic scope

2019 ◽  
Vol 8 (3) ◽  
pp. 432-446
Author(s):  
María Elena Bravo-Gómez ◽  
Laura Nayeli Camacho-García ◽  
Luz Alejandra Castillo-Alanís ◽  
Miguel Ángel Mendoza-Meléndez ◽  
Alejandra Quijano-Mateos
Keyword(s):  
Pharmacokinetic Model ◽  
Pbpk Model ◽  
Whole Body ◽  
Physiologically Based Pharmacokinetic Model ◽  
Time Profiles ◽  
Physiologically Based Pharmacokinetic ◽  
Concentration Time ◽  
Physiologically Based ◽  
Permeability Rate ◽  
Different Tissues

A whole-body permeability-rate-limited physiologically based pharmacokinetic (PBPK) model for cocaine was developed with the aim to predict the concentration–time profiles of the drug in blood and different tissues in humans.

scholarly journals Physiologically Based Pharmacokinetic Models of Probenecid and Furosemide to Predict Transporter Mediated Drug-Drug Interactions

2020 ◽  
Vol 37 (12) ◽  
Author(s):  
Hannah Britz ◽  
Nina Hanke ◽  
Mitchell E. Taub ◽  
Ting Wang ◽  
Bhagwat Prasad ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Organic Anion ◽  
Plasma Concentrations ◽  
Whole Body ◽  
Time Profiles ◽  
Pbpk Models ◽  
Physiologically Based Pharmacokinetic ◽  
Concentration Time ◽  
Anion Transporter ◽  
Physiologically Based

Abstract Purpose To provide whole-body physiologically based pharmacokinetic (PBPK) models of the potent clinical organic anion transporter (OAT) inhibitor probenecid and the clinical OAT victim drug furosemide for their application in transporter-based drug-drug interaction (DDI) modeling. Methods PBPK models of probenecid and furosemide were developed in PK-Sim®. Drug-dependent parameters and plasma concentration-time profiles following intravenous and oral probenecid and furosemide administration were gathered from literature and used for model development. For model evaluation, plasma concentration-time profiles, areas under the plasma concentration–time curve (AUC) and peak plasma concentrations (Cmax) were predicted and compared to observed data. In addition, the models were applied to predict the outcome of clinical DDI studies. Results The developed models accurately describe the reported plasma concentrations of 27 clinical probenecid studies and of 42 studies using furosemide. Furthermore, application of these models to predict the probenecid-furosemide and probenecid-rifampicin DDIs demonstrates their good performance, with 6/7 of the predicted DDI AUC ratios and 4/5 of the predicted DDI Cmax ratios within 1.25-fold of the observed values, and all predicted DDI AUC and Cmax ratios within 2.0-fold. Conclusions Whole-body PBPK models of probenecid and furosemide were built and evaluated, providing useful tools to support the investigation of transporter mediated DDIs.

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