Development of a novel method for predicting human volume of distribution at steady-state of basic drugs and comparative assessment with existing methods

Poulin, Patrick; Theil, Frank‐Peter

doi:10.1002/jps.21759

Cited by 104 publications

(110 citation statements)

References 24 publications

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“…There are several other approaches [25][26][27][28][29] for the estimation of human pharmaco-kinetics and various tissue distributions, such as physiological based pharmaco-kinetic modelling (PBPK) using various physico-chemical, preclinical and in vivo data, 30 which are outside the scope of our approach.…”

Section: Introductionmentioning

confidence: 99%

Estimating Unbound Volume of Distribution and Tissue Binding by In Vitro HPLC-Based Human Serum Albumin and Immobilised Artificial Membrane-Binding Measurements

Valkó

Nunhuck

Hill

2011

Journal of Pharmaceutical Sciences

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Section: Introductionmentioning

confidence: 99%

Estimating Unbound Volume of Distribution and Tissue Binding by In Vitro HPLC-Based Human Serum Albumin and Immobilised Artificial Membrane-Binding Measurements

Valkó

Nunhuck

Hill

2011

Journal of Pharmaceutical Sciences

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“…Recently, unified algorithms combining these different processes have been developed to facilitate their application (6,(46)(47)(48). Several studies have been performed to explore predictability of the different mechanistic approaches for Kp prediction using diverse drug datasets, with varying degrees of accuracy (8,10,11,(48)(49)(50)(51)(52)(53).…”

Section: Pbpk Model Methodologies Small Molecule Pbpk Modelsmentioning

confidence: 99%

Dose Selection Based on Physiologically Based Pharmacokinetic (PBPK) Approaches

Jones

Mayawala

Poulin³

2012

AAPS J

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Abstract. Physiologically based pharmacokinetic (PBPK) models are built using differential equations to describe the physiology/anatomy of different biological systems. Readily available in vitro and in vivo preclinical data can be incorporated into these models to not only estimate pharmacokinetic (PK) parameters and plasma concentration-time profiles, but also to gain mechanistic insight into compound properties. They provide a mechanistic framework to understand and extrapolate PK and dose across in vitro and in vivo systems and across different species, populations and disease states. Using small molecule and large molecule examples from the literature and our own company, we have shown how PBPK techniques can be utilised for human PK and dose prediction. Such approaches have the potential to increase efficiency, reduce the need for animal studies, replace clinical trials and increase PK understanding. Given the mechanistic nature of these models, the future use of PBPK modelling in drug discovery and development is promising, however some limitations need to be addressed to realise its application and utility more broadly.

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“…A limitation of the approach is that, whereas tissue composition is well defined for the rat, detailed human data are relatively www.annualreviews.org • Physiologically-Based Pharmacokinetics deficient. Although there are similarities, there are also some important differences in the acidic phospholipid content of some tissues that should be taken into account (97,98).…”

Section: Prediction Of Drug Distributionmentioning

confidence: 96%

“…Tested against this global parameter, the in vitro tissue model predicted observations in humans reasonably well (98,99) (Figure 6), although some clear outliers indicate the need for further research. Transporters are not included in the general PBPK tissue model, which also assumes a simple perfusion-rate limitation.…”

Section: Prediction Of Drug Distributionmentioning

confidence: 96%

Physiologically-Based Pharmacokinetics in Drug Development and Regulatory Science

Rowland

Peck

Tucker

2011

Annu. Rev. Pharmacol. Toxicol.

588

442

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The application of physiologically-based pharmacokinetic (PBPK) modeling is coming of age in drug development and regulation, reflecting significant advances over the past 10 years in the predictability of key pharmacokinetic (PK) parameters from human in vitro data and in the availability of dedicated software platforms and associated databases. Specific advances and contemporary challenges with respect to predicting the processes of drug clearance, distribution, and absorption are reviewed, together with the ability to anticipate the quantitative extent of PK-based drug-drug interactions and the impact of age, genetics, disease, and formulation. The value of this capability in selecting and designing appropriate clinical studies, its implications for resource-sparing techniques, and a more holistic view of the application of PK across the preclinical/clinical divide are considered. Finally, some attention is given to the positioning of PBPK within the drug development and approval paradigm and its future application in truly personalized medicine.

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Development of a novel method for predicting human volume of distribution at steady-state of basic drugs and comparative assessment with existing methods

Cited by 104 publications

References 24 publications

Estimating Unbound Volume of Distribution and Tissue Binding by In Vitro HPLC-Based Human Serum Albumin and Immobilised Artificial Membrane-Binding Measurements

Estimating Unbound Volume of Distribution and Tissue Binding by In Vitro HPLC-Based Human Serum Albumin and Immobilised Artificial Membrane-Binding Measurements

Dose Selection Based on Physiologically Based Pharmacokinetic (PBPK) Approaches

Physiologically-Based Pharmacokinetics in Drug Development and Regulatory Science

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