PhRMA CPCDC initiative on predictive models of human pharmacokinetics, part 3: Comparative assessement of prediction methods of human clearance

Ring, Barbara J.; Chien, Jenny Y.; Adkison, Kimberly K.; Jones, Hannah M.; Rowland, Malcolm; Jones, Rhys D.O.; Yates, James; Ku, M. Sherry; Gibson, Christopher R; He, Handan; Vuppugalla, Ragini; Marathe, Punit; Fischer, Volker; Dutta, Sandeep; Sinha, Vikash; Bjornsson, Thorir D.; Lavé, Thierry; Poulin, Patrick

doi:10.1002/jps.22552

Cited by 173 publications

(211 citation statements)

References 25 publications

(113 reference statements)

Supporting

Mentioning

201

Contrasting

Order By: Relevance

“…Of course, this is not a trivial problem [1][2][3][4][5] because different values for the same parameter can be found in the literature due, in some cases to considerable inter-subjects variability [23 -29]. Accordingly, in order to simplify comparison of the three different drugs considered in this paper (theophylline, temazepam and nimesulide), we decided to rely exclusively on the information reported in [10] as source of PK parameters values.…”

Section: Resultsmentioning

confidence: 99%

“…Its chemical/physical and PK characteristics are reported in Table 1. Figure 2A shows the results of model simulations when assuming an orally administered dose of 100 mg dispersed in a polymeric carrier with a volume of 1 cm 3 . In particular, the continuous thick solid line refers to theophylline concentration in the plasma (C p ) in the case of only one spherical matrix of 6200 m radius.…”

Section: Resultsmentioning

confidence: 99%

“…Quite recently, an initiative of the Pharmaceutical Research and Manufacturers of America (PhRMA) tried to evaluate the reliability of predictive models in terms of of drug efficacy, safety and properties estimation [1][2][3]. For this purpose, 108 clinical compounds (22 % acids, 46 % bases, 18 % zwitterions and 14 % neutrals), supplied by 12 PhRMA member companies, have been considered.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A physiologically oriented mathematical model for the description of in vivo drug release and absorption

Cont¹,

Abrami²,

Hasa³

et al. 2014

ADMET DMPK

View full text Add to dashboard Cite

This paper focuses on a physiologically-oriented mathematical model aimed at studying the in vivo drug release, absorption, distribution, metabolism and elimination (ADME). To this purpose, the model accounts for drug delivery from an ensemble of non-eroding poly-disperse polymeric particles and the subsequent ADME processes. The model outcomes are studied with reference to three widely used drugs: theophylline, temazepam and nimesulide. One of the most important results of this study is the quantitative evaluation of the interplay between the release kinetics and the subsequent ADME processes. Indeed, it is usually assumed that in vivo drug release coincides with in vitro so that the effect exerted by the ADME processes is neglected. In addition, the proposed model may be an important tool for the design of delivery systems since, through proper changes, it could also account for different oral delivery systems.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A physiologically oriented mathematical model for the description of in vivo drug release and absorption

Cont¹,

Abrami²,

Hasa³

et al. 2014

ADMET DMPK

View full text Add to dashboard Cite

show abstract

“…Since one of the traditional foundations of PBPK modelling is the IVIVE of ADME processes, the selection of the extrapolation model by software developers or model-writers can have a huge impact on the success of predictions. A recently published initiative of the Pharmaceutical Research and Manufacturers of America (PhRMA) aimed to assess the performance of various ADME prediction methods and models in the prediction of human pharmacokinetics from preclinical and in vitro data [54][55][56][57][58]. This extensive evaluation concluded that, for the compound dataset studied, the PBPK approach generally poorly predicted the distribution, and the absorption, or intestinal and hepatic first-pass clearance.…”

Section: Discussionmentioning

confidence: 99%

Physiologically based pharmacokinetic (PBPK) modelling tools: how to fit with our needs?

Bouzom

Ball

Perdaems

et al. 2012

Biopharm & Drug Disp

View full text Add to dashboard Cite

In 2005, a survey compared a number of commercial PBPK software available at the time, mainly focusing on 'ready to use' modelling tools. Since then, these tools and software have been further developed and improved to allow modellers to perform WB-PBPK modelling including ADME processes at a high level of sophistication. This review presents a comparison of the features, values and limitations of both the 'ready to use' software and of the traditional user customizable software that are frequently used for the building and use of PBPK models, as well as the challenges associated with the various modelling approaches regarding their current and future use. PBPK models continue to be used more and more frequently during the drug development process since they represent a quantitative, physiologically realistic platform with which to simulate and predict the impact of various potential scenarios on the pharmacokinetics and pharmacodynamics of drugs. The 'ready to use' PBPK software has been a major factor in the increasing use of PBPK modelling in the pharmaceutical industry, opening up the PBPK approach to a broader range of users. The challenge is now to educate and to train scientists and modellers to ensure their appropriate understanding of the assumptions and the limitations linked both to the physiological framework of the 'virtual body' and to the scaling methodology from in vitro to in vivo (IVIVE).

show abstract

“…It also helps obtain preliminary data on the metabolism of a drug candidate. This is termed metabolic profiling 22 . In future, combination of microdosing and modelling may lead to more reliable predictions in new drug development.…”

Section: Applications Of Micro Dosingmentioning

confidence: 99%

Human Micro Dosing Studies (Phase 0): A Novel Approach in Clinical Research

Aiswarya¹,

Manohar²

2014

J Pharm Sci Innov.

View full text Add to dashboard Cite

Micro dosing or Phase 0 clinical trial is a breakthrough in drug development, where sub therapeutic dosages of various investigational products are administered under necessary safety conditions to minimal number of volunteers in order to obtain an early pharmacokinetic profile of the product. This important important bioanlaytic tool benefits patients as well as the pharmaceutical industry by bringing out new effective molecules faster and reducing the attrition rates at later clinical trial phases. This review encompasses the concept of micro dosing from its inception to its practical approaches till date in clinical research. The concept has evolved over the last decade from merely pharmacokinetic assessments to wider perspectives like drug-drug, drug-food interactions, bioavailability, oncology, metabolic profiling and use in vulnerable populations etc. which are discussed in this article. In future, micro dosing might emerge to be the standard predictive tool for human pharmacokinetics over alternative method and may continue to provide benefits that aren't fully realized up to date.

show abstract

PhRMA CPCDC initiative on predictive models of human pharmacokinetics, part 3: Comparative assessement of prediction methods of human clearance

Cited by 173 publications

References 25 publications

A physiologically oriented mathematical model for the description of in vivo drug release and absorption

A physiologically oriented mathematical model for the description of in vivo drug release and absorption

Physiologically based pharmacokinetic (PBPK) modelling tools: how to fit with our needs?

Human Micro Dosing Studies (Phase 0): A Novel Approach in Clinical Research

Contact Info

Product

Resources

About