Physiologically based pharmacokinetic modelling 2: Predicting the tissue distribution of acids, very weak bases, neutrals and zwitterions

Rodgers, Trudy; Rowland, Malcolm

doi:10.1002/jps.20502

Cited by 801 publications

(847 citation statements)

References 48 publications

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“…The organ‐to‐plasma partition coefficients were determined using drug physicochemical properties based on methods described by Rodgers et al 20. and Rodgers and Rowland 20, 21…”

Section: Methodsmentioning

confidence: 99%

Physiologically Based Pharmacokinetic Approach to Determine Dosing on Extracorporeal Life Support: Fluconazole in Children on ECMO

Watt

Cohen‐Wolkowiez

Barrett

et al. 2018

CPT Pharmacom & Syst Pharma

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Extracorporeal life support (e.g., dialysis, extracorporeal membrane oxygenation (ECMO)) can affect drug disposition, placing patients at risk for therapeutic failure. In this population, dose selection to achieve safe and effective drug exposure is difficult. We developed a novel and flexible approach that uses physiologically based pharmacokinetic (PBPK) modeling to translate results from ECMO ex vivo experiments into bedside dosing recommendations. To determine fluconazole dosing in children on ECMO, we developed a PBPK model, which was validated using fluconazole pharmacokinetic (PK) data in adults and critically ill infants. Next, an ECMO compartment was added to the PBPK model and parameterized using data from a previously published ex vivo study. Simulations using the final ECMO PBPK model reasonably characterized observed PK data in infants on ECMO, and the model was used to derive dosing in children on ECMO across the pediatric age spectrum. This approach can be generalized to other forms of extracorporeal life support (ECLS), such as dialysis.

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“…The organ‐to‐plasma partition coefficients were determined using drug physicochemical properties based on methods described by Rodgers et al 20. and Rodgers and Rowland 20, 21…”

Section: Methodsmentioning

confidence: 99%

Physiologically Based Pharmacokinetic Approach to Determine Dosing on Extracorporeal Life Support: Fluconazole in Children on ECMO

Watt

Cohen‐Wolkowiez

Barrett

et al. 2018

CPT Pharmacom & Syst Pharma

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“…The volume of distribution at steady state was calculated by the tissue partition coefficient using the equation described by the Rodgers et al 17, 18. and the Rodgers & Rowland19, 20 methods considering the rapid equilibrium between blood and tissues.…”

Section: Methodsmentioning

confidence: 99%

Prediction of the Pharmacokinetics of Pravastatin as an OATP Substrate Using Plateable Human Hepatocytes With Human Plasma Data and PBPK Modeling

Mao¹,

Doshi

Wright³

et al. 2018

CPT Pharmacom & Syst Pharma

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Plateable human hepatocytes with human plasma were utilized to generate the uptake transporter kinetic data for pravastatin, an organic anion‐transporting polypeptide (OATP) transporter substrate. The active hepatic uptake of pravastatin was determined with a Jmax value of 134.4 pmol/min/million cells and Km of 76.77 µM in plateable human hepatocytes with human plasma. The physiologically‐based pharmacokinetic (PBPK) model with incorporation of these in vitro kinetic data successfully simulated the i.v. pharmacokinetic profile of pravastatin without applying scaling factor (the mean predicted area under the curve (AUC) is within 1.5‐fold of the observed). Furthermore, the PBPK model also adequately described the oral plasma concentration‐time profiles of pravastatin at different dose levels. The current investigation demonstrates an approach allowing us to build upon the translation of in vitro OATP uptake transporter data to in vivo, with a hope of utilizing the in vitro data for the prospective human pharmacokinetic (PK) prediction.

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“…Last, the physiological parameters required to calculate the tissue‐to‐plasma partition coefficients by the PK‐Sim standard method1, 2 and the method by Rodgers et al 3. and Rogers and Rowland4 were identified from the literature sources. The literature search was performed using PubMed and/or Google Scholar.…”

Section: Methodsmentioning

confidence: 99%

“…Table 1, 1, 2, 3, 4,9, 10, 11, 12, 13, 14, 15 summarizes all processes and input parameters relevant for the PBPK models of the six test compounds. A more detailed description of the test compounds and the respective PBPK models can be found in the Supplementary Section SI .…”

Section: Methodsmentioning

confidence: 99%

“…One reason is the inconsistent use of the organ model structures across publications (e.g., blood‐flow limited and permeability limited distribution, active transport processes). Second, these models do not make use of established in silico methods to predict the tissue‐to‐plasma partition coefficients 1, 2, 3, 4. As a result, currently, little attention has been shown to the precise handling of organs relevant for toxicity assessment in a generic PBPK model.…”

Section: Study Highlightsmentioning

confidence: 99%

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Development of Physiologically Based Organ Models to Evaluate the Pharmacokinetics of Drugs in the Testes and the Thyroid Gland

Pilari

Gaub

Block

et al. 2017

CPT Pharmacometrics Syst. Pharmacol.

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We extended a generic whole‐body physiologically based pharmacokinetic (PBPK) model for rats and humans for organs of the reproductive and endocrine systems (i.e., the testes and the thyroid gland). An extensive literature search was performed, first, to determine the most generic organ model structures for testes and thyroid across species, and, second, to identify the corresponding anatomic and physiological parameters in rats and humans. The testes and thyroid organ models were implemented in the PBPK modeling software PK‐Sim and MoBi. The capability of the PBPK approach to simulate the testes and thyroid tissue concentration data was demonstrated using a series of test compounds. The presented organ model structures and parameterization yielded a close agreement between observed and simulated tissue concentrations over time. The organ models are ready to be used to predict the pharmacokinetics of passively entering drugs in the testes and thyroid tissue in a generic PBPK modeling framework.

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Physiologically based pharmacokinetic modelling 2: Predicting the tissue distribution of acids, very weak bases, neutrals and zwitterions

Cited by 801 publications

References 48 publications

Physiologically Based Pharmacokinetic Approach to Determine Dosing on Extracorporeal Life Support: Fluconazole in Children on ECMO

Physiologically Based Pharmacokinetic Approach to Determine Dosing on Extracorporeal Life Support: Fluconazole in Children on ECMO

Prediction of the Pharmacokinetics of Pravastatin as an OATP Substrate Using Plateable Human Hepatocytes With Human Plasma Data and PBPK Modeling

Development of Physiologically Based Organ Models to Evaluate the Pharmacokinetics of Drugs in the Testes and the Thyroid Gland

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