The Phoenix Model object uses NLME (non-linear mixed effects) to enable users to perform a variety of pharmacokinetic and pharmacodynamic analyses using individual and population modeling. It provides access to several robust and efficient Maximum Likelihood engines to perform individual, population, and pooled data analyses (e.g., Naive Pool, FOCE, QRPEM, ...), It also offers a non-parametric engine. Phoenix NLME provides automated covariate selection, bootstrap, and visual predictive check options. It creates consistent graphical and worksheet output to allow easy comparison between models via the Phoenix NLME Model Comparer object.
Note:Phoenix NLME is only supported on 64-bit systems.
Users have three ways for creating a custom PK model.
•The built-in model uses the menus in the Phoenix Model object to create a model, which is customizable to the extent that various options and selections may be combined at the user's discretion.
•The graphical model uses the graphical model editor to create the model structure in diagram form. (Refer to “Graphical model interface” for more details.)
•The textual model allows users to write their own model using PML (Phoenix Modeling Language), which allows for the greatest amount of flexibility in model structure and customization. (See “Textual model interface” for more information.)
Combinations of these three methods may be necessary to build the desired model. For example, when preparing a recycling model (enterohepatic recirculation), a graphical model can be built, but textual changes must be made to complete the model, such as:
•Add a function, called switch, to turn on and off the recycling process.
double(Switch)
•Adjust the structural model equations to use the Rate variable.
deriv(Abile=(A1*K1g)-(Abile*Rate))
deriv(Agut=(Abile*Rate)-(Agut*Ka))
Rate=Switch/Tau #Tau is the gall bladder emptying interval
• Add a sequence block to define the gall bladder emptying process.
Ri=10 #Time recirculation occurs, 10hrs used here
sequence{
Switch=0; #Turn off the gall bladder emptying
sleep(Ri); #Wait for 10 hours
Switch=1; #Turn on the gall bladder emptying on
sleep(Tau); #Wait for the gall bladder emptying interval
Switch=0; #Turn off the gall bladder emptying
}
•Add fixed effect for Tau.
fixef(Tau=c(, 3,))
•Comment out any unused parameters and adjust fixed effect values as needed.
Caution:In the NLME interface, where numbers can be entered in data fields, generally either comma (,) or period (.) can be used as a decimal point. (It will be converted to a period.) However, there are fields where sequences of numbers, separated by commas, can be entered, such as the sequence of times in a table specification. In those fields, the comma character cannot be used as a decimal point, because it acts as a delimiter between numbers.
The following symbol in the Phoenix NLME documentation indicates information specific to individual modeling,
This section contains information on the following topics:
