Mechanistic Approaches to Volume of Distribution Predictions: Understanding the Processes

Rodgers, Trudy; Rowland, Malcolm

doi:10.1007/s11095-006-9210-3

Cited by 359 publications

(355 citation statements)

References 97 publications

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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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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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show abstract

“…For comparison, V ss was also calculated according to the tissue composition equations proposed by Poulin and Theil (2002) and Rodgers and Rowland (2007). These tissue composition equations are considered to be mechanistic alternatives to interspecies scaling and facilitate the use of physiologically based pharmacokinetic models in the absence of in vivo tissue distribution data.…”

Section: Berry Et Almentioning

confidence: 99%

“…The present work aims to do so. Finally, interspecies scaling methods were compared with the mechanistic tissue partition methods for prediction of human V ss proposed by Poulin and Theil (2002) and Rodgers and Rowland (2007).…”

Section: Introductionmentioning

confidence: 99%

Species Differences in Distribution and Prediction of HumanV_ssfrom Preclinical Data

Berry¹,

Li²,

Zhao³

2011

Drug Metab Dispos

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ABSTRACT:Prediction of human volume of distribution at steady state (V ss ) before first administration of a new drug candidate to humans has become an important part of the drug development process. This study examines the assumptions behind interspecies scaling techniques used to predict human V ss from preclinical data, namely the equivalency of V ss,u and/or f ut across species. In addition, several interspecies scaling techniques are evaluated side by side using a set of 67 reference compounds where observed V ss from rats, dogs, monkeys, and humans were compiled from the literature and where plasma protein binding was determined across species using an ultracentrifugation technique. Species similarity in V ss,u or f ut does not appear to be the norm among rats, dogs, monkeys, or humans. Despite this, interspecies scaling from rats, dogs, and monkeys is useful and can provide reasonably accurate predictions of human V ss , although some interspecies scaling approaches were better than others. For example, the performance of the common V ss,u or f ut equivalency approaches using average V ss,u or f ut across three preclinical species was superior to allometric scaling techniques. In addition, considering data from several preclinical species, using the equivalency approach, was superior to scaling from any single species. Although the mechanistic tissue composition equations available in the Simcyp populationbased pharmacokinetic simulator did not necessarily provide the most accurate predictions, and the equations used likely need refinement, they still provide the best opportunity for a mechanistic understanding and prediction of human V ss .

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“…In order to estimate the unknown association constants, Rodgers et al suggested to determine K A,AP for the erythrocytes from the blood-plasma ratio B : P and use this value as an approximation for the association constants in the other tissues. For details see (12,26). Parameter values can be found in (12,16) for the species rat.…”

Section: Resultsmentioning

confidence: 99%

“…(13)). Parameter values can be found in (16,26) for the species rat. In their seminal papers in 2000/01 (13,14), Poulin and Theil proposed an in silico approach to a priori predict tissue-plasma partition coefficients solely based on few compound specific in vitro data.…”

Section: Very Weak Bases Neutrals Acids and Type 2 Zwitterionsmentioning

confidence: 99%

Physiologically based pharmacokinetic modelling: a sub-compartmentalized model of tissue distribution

Kleist

Huisinga²

2007

J Pharmacokinet Pharmacodyn

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We present a sub-compartmentalized model of drug distribution in tissue that extends existing approaches based on the well-stirred tissue model. It is specified in terms of differential equations that explicitly account for the drug concentration in erythrocytes, plasma, interstitial and cellular space. Assuming, in addition, steady state drug distribution and by lumping the different sub-compartments, established models to predict tissue-plasma partition coefficients can be derived in an intriguingly simple way. This direct link is exploited to explicitly construct and parameterize the sub-compartmentalized model for moderate to strong bases, acids, neutrals and zwitterions. The derivation highlights the contributions of the different tissue constituents and provides a simple and transparent framework for the construction of novel tissue distribution models.

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Mechanistic Approaches to Volume of Distribution Predictions: Understanding the Processes

Cited by 359 publications

References 97 publications

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

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

Species Differences in Distribution and Prediction of HumanV_ssfrom Preclinical Data

Physiologically based pharmacokinetic modelling: a sub-compartmentalized model of tissue distribution

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Mechanistic Approaches to Volume of Distribution Predictions: Understanding the Processes

Cited by 359 publications

References 97 publications

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

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

Species Differences in Distribution and Prediction of HumanVssfrom Preclinical Data

Physiologically based pharmacokinetic modelling: a sub-compartmentalized model of tissue distribution

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Product

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Species Differences in Distribution and Prediction of HumanV_ssfrom Preclinical Data