PML - Dosing

Dosing

Dosing can be specified in two places, the model file and the column definition file. For more, see “Modeling Project Files”.

In the model, the dosepoint statement specifies the compartment that can receive dose. Its syntax is given by:

  dosepoint(CompartmentName
     [, tlag = expr]
     [, duration = expr]
     [, rate = expr]
     [, bioavail = expr]
     )

The options tlag, duration, rate, and bioavail are optional and their meanings are given as follows:

tlag=expr: dose delivery is delayed by expr
duration=expr: zero-order absorption with duration spanning expr time units
rate=expr: zero-order absorption with rate being expr mass unit/time unit
bioavail=expr: the fraction of dose absorbed is expr

The dosepoint statement can also include statements to be executed right before and/or after delivery of the dose, as follows.

dobefore=block
doafter=block

A block refers to a pair of curly brackets {...} with zero or more statements in between them. For more information on dobefore and doafter, see “Action code”.

Covariates

Covariates can be simple or interpolated. See “Modeling Project Files” for more information.

covariate(covariate_name)

This specifies that there is a covariate with the given name. For time-varying covariates, the covariate statement extrapolates backward. So, for example, if a covariate is given at time=1, 2, and 3 to be 10, 20, and 30, respectively, then the covariate value in [0,1] is 10, in [1,2] is 20, and in [2,3] is 30.

fcovariate(covariate_name)

This is the same as covariate, except that it also specifies the covariate has forward direction. fcovariate extrapolates forward. So, for example, if a covariate is given at time=1, 2, and 3 to be 10, 20, and 30, respectively, the fcovariate value for [1,2] is 10, for [2,3] is 20, and for times beyond 3 (if any) it is 30. If no covariate value is given at time=0, the fcovariate value for [0,1] is also 10, as the first value propagates backward as well as forward.

There are actually two different ways to indicate forward direction, by using the fcovariate statement in the model text, or by using fcovr in the column definition text (or both).

interpolate(covariate_name)

This also specifies that there is a covariate with the given name, however, the value of the covariate varies linearly between time points at which it is set in time-based models. This feature should be used with caution, because in some cases it makes a linear model nonlinear so it cannot use the matrix exponent ODE solver.

This can happen in a simple PK model parameterized by Cl and V, if V is a function of bodyweight BW, and BW is interpolated. Alternatively if the model is parameterized by Ke and V, it is not affected because V does not enter the differential equations.

covariate(Form())

In a text model, if a covariate is categorical, its name must be followed by empty parentheses. This informs the UI that the covariate is categorical, and thus available for stratification.