Physiologically based pharmacokinetic modelling of human exposure to 2-butoxyethanol

Franks, S.J.; Spendiff, Martin; Cocker, John; Loizou, George

doi:10.1016/j.toxlet.2005.09.012

Cited by 23 publications

(14 citation statements)

References 9 publications

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“…A human PBPK model describing a bladder compartment to simulate fluctuations in metabolite concentration in urine caused by micturition (Franks et al, 2006), was adapted to study the inhalation pharmacokinetics of m -xylene (Figure 1). Liver, adipose, richly and slowly perfused tissues, and the bladder represents the body.…”

Section: Methodsmentioning

confidence: 99%

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A Workflow for Global Sensitivity Analysis of PBPK Models

McNally¹,

Cotton²,

Loizou³

2011

Front. Pharmacol.

107

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Physiologically based pharmacokinetic (PBPK) models have a potentially significant role in the development of a reliable predictive toxicity testing strategy. The structure of PBPK models are ideal frameworks into which disparate in vitro and in vivo data can be integrated and utilized to translate information generated, using alternative to animal measures of toxicity and human biological monitoring data, into plausible corresponding exposures. However, these models invariably include the description of well known non-linear biological processes such as, enzyme saturation and interactions between parameters such as, organ mass and body mass. Therefore, an appropriate sensitivity analysis (SA) technique is required which can quantify the influences associated with individual parameters, interactions between parameters and any non-linear processes. In this report we have defined the elements of a workflow for SA of PBPK models that is computationally feasible, accounts for interactions between parameters, and can be displayed in the form of a bar chart and cumulative sum line (Lowry plot), which we believe is intuitive and appropriate for toxicologists, risk assessors, and regulators.

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Section: Methodsmentioning

confidence: 99%

“…To imitate micturition, the bladder is assumed to fill with urine at a constant (but adjustable) rate and empty at discrete time intervals (when the volume of urine reduces to zero). This enables comparison to be made between model predictions and experimental observations with timed sampling in human volunteer studies (Franks et al, 2006). …”

Section: Methodsmentioning

confidence: 99%

A Workflow for Global Sensitivity Analysis of PBPK Models

McNally¹,

Cotton²,

Loizou³

2011

Front. Pharmacol.

107

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“…Going forward it is possible that one may be able to evaluate species differences and incorporate such information in human PK and dose projections (60,61). Similarly, the increased availability of computing power and software packages has enabled the development of PB/PK-based models (42,62,63). Such physiological models allow one to conduct extrapolations across species in a more mechanistic fashion.…”

Section: Conclusion and Future Directionmentioning

confidence: 99%

Projection of Exposure and Efficacious Dose Prior to First-in-Human Studies: How Successful Have We Been?

Huang

Zheng²,

Yang

et al. 2007

Pharm Res

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“…Physiologically based pharmacokinetics (PBPK) modelling has been developed to predict the level of total BAA in urine after exposure to 2-BE in air (through both inhalation and dermal contact) 17. Based on the model, for the W1 exposure of 1.89 ppm, the predicted value of total BAA is about 20 mg/g creatinine.…”

Section: Discussionmentioning

confidence: 99%