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A Tutorial on Pharmacodynamic Scripting Facility in   Simcyp

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The Simcyp Simulator provides a framework for mechanistic Physiologically‐Based Pharmacokinetic/Pharmacodynamic modeling of potentially interacting drugs... Examples incorporating differential equations and including inter‐individual variability on parameters are presented... To incorporate inter‐individual variability, the Simcyp Simulator generates virtual populations of individuals from models incorporating structural correlation of multiple factors (including demographics, genetic and disease status) generating an individual subject with its own set of parameters. 1 A more mechanistic simulation approach can incorporate model components that account for and predict individual covariates... These models can represent a kinetic receptor binding model and be transduced to a stimulus response model in a subsequent PD Basic unit... The PD Link unit includes transform link models, which are simple transforms to convert response to a probability or event count rate, and parameterised link models which include indirect response models6 and survival models. 7 The PD Link unit does not include the effect compartment or kinetic receptor binding links as these models are available in the PD Basic unit... sc:setParameter(1,VKORC1) We have coded here a covariate that was found to affect IC50... Such sc:set functions store values at the same scoping level as the function within which they occur ( The sc:get functions try the same level and if the parameter information is not found, go to the next higher scoping level to find the information... sc:setIIVDistribution(3, sc.NORMAL_SD, 45, 0) – Emax sc:setIIVDistribution(4, sc.NORMAL_SD, 0.1, 0) – effect of age EMAX = P[3] * (1+ P[5]) AGEF = P[4]*(sc:getIndivAge ‐ 45) – effect of age on baseline response Furthermore, a freely available R library package has recently been developed to enable a user to run Simcyp directly from the R environment, commonly used for statistical scripting (a similar interfacing facility has been developed for the Matlab environment). 15 This will allow further manipulation of Simcyp parameters from these computing platforms and so could potentially be used for fitting Lua‐coded models as well... A scripting facility for customising PD response models within the Simcyp Simulator has been developed, whereby a user can replace the built‐in model for a given PD step with a script using a dedicated editor.

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A screenshot of the Simcyp Lua Editor shows the Functions dropdown menu. The expanded menu shows how to access various get functions templates to get individual covariates.
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psp412102-fig-0003: A screenshot of the Simcyp Lua Editor shows the Functions dropdown menu. The expanded menu shows how to access various get functions templates to get individual covariates.

Mentions: Within a script, there are named script functions (e.g. “Step” and “Setup” functions) which are called by the Simulator platform at specific points in the simulation. Such functions are generically known to programmers as “call‐back” functions. Simcyp maintains the signatures of these call‐back functions and uses them to give controlled access to inputs and parameters through function arguments and the values to be passed onto as the function's return value. The particular function names are reserved and a particular signature is required for the function to be valid. Coding of Lua scripts is supported by a “Functions” dropdown menu, which provides templates for calls to Simcyp Library functions (calls to Simcyp C++ code available as Lua script functions) as well as function definition templates for user‐coded Lua Setup and Step functions (Figure3; see also Supplementary Materials for additional functions in the dropdown menu).


A Tutorial on Pharmacodynamic Scripting Facility in   Simcyp
A screenshot of the Simcyp Lua Editor shows the Functions dropdown menu. The expanded menu shows how to access various get functions templates to get individual covariates.
© Copyright Policy - creativeCommonsBy-nc
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5036420&req=5

psp412102-fig-0003: A screenshot of the Simcyp Lua Editor shows the Functions dropdown menu. The expanded menu shows how to access various get functions templates to get individual covariates.
Mentions: Within a script, there are named script functions (e.g. “Step” and “Setup” functions) which are called by the Simulator platform at specific points in the simulation. Such functions are generically known to programmers as “call‐back” functions. Simcyp maintains the signatures of these call‐back functions and uses them to give controlled access to inputs and parameters through function arguments and the values to be passed onto as the function's return value. The particular function names are reserved and a particular signature is required for the function to be valid. Coding of Lua scripts is supported by a “Functions” dropdown menu, which provides templates for calls to Simcyp Library functions (calls to Simcyp C++ code available as Lua script functions) as well as function definition templates for user‐coded Lua Setup and Step functions (Figure3; see also Supplementary Materials for additional functions in the dropdown menu).

View Article: PubMed Central - PubMed

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

The Simcyp Simulator provides a framework for mechanistic Physiologically‐Based Pharmacokinetic/Pharmacodynamic modeling of potentially interacting drugs... Examples incorporating differential equations and including inter‐individual variability on parameters are presented... To incorporate inter‐individual variability, the Simcyp Simulator generates virtual populations of individuals from models incorporating structural correlation of multiple factors (including demographics, genetic and disease status) generating an individual subject with its own set of parameters. 1 A more mechanistic simulation approach can incorporate model components that account for and predict individual covariates... These models can represent a kinetic receptor binding model and be transduced to a stimulus response model in a subsequent PD Basic unit... The PD Link unit includes transform link models, which are simple transforms to convert response to a probability or event count rate, and parameterised link models which include indirect response models6 and survival models. 7 The PD Link unit does not include the effect compartment or kinetic receptor binding links as these models are available in the PD Basic unit... sc:setParameter(1,VKORC1) We have coded here a covariate that was found to affect IC50... Such sc:set functions store values at the same scoping level as the function within which they occur ( The sc:get functions try the same level and if the parameter information is not found, go to the next higher scoping level to find the information... sc:setIIVDistribution(3, sc.NORMAL_SD, 45, 0) – Emax sc:setIIVDistribution(4, sc.NORMAL_SD, 0.1, 0) – effect of age EMAX = P[3] * (1+ P[5]) AGEF = P[4]*(sc:getIndivAge ‐ 45) – effect of age on baseline response Furthermore, a freely available R library package has recently been developed to enable a user to run Simcyp directly from the R environment, commonly used for statistical scripting (a similar interfacing facility has been developed for the Matlab environment). 15 This will allow further manipulation of Simcyp parameters from these computing platforms and so could potentially be used for fitting Lua‐coded models as well... A scripting facility for customising PD response models within the Simcyp Simulator has been developed, whereby a user can replace the built‐in model for a given PD step with a script using a dedicated editor.

No MeSH data available.