Estimate starting parameters using PKNCA

Usage

# S3 method for class 'pknca'
nlmixr2Est(env, ...)

Arguments

env

Environment for the nlmixr2 estimation routines.

This needs to have:

- rxode2 ui object in `$ui`

- data to fit in the estimation routine in `$data`

- control for the estimation routine's control options in `$ui`

...

Other arguments provided to `nlmixr2Est()` provided for flexibility but not currently used inside nlmixr

Value

A model with updated starting parameters. In the model a new element named "nca" will be available which includes the PKNCA results used for the calculation.

Details

Parameters are estimated as follows:

ka 4 half-lives to Tmax but not higher than 3: log(2)/(tmax/4)
vc Inverse of dose-normalized Cmax
cl Estimated as the median clearance
vp,vp22- and 4-fold the vc, respectively by default, controlled by the vpMult and vp2Mult arguments to pkncaControl
q,q2 0.5- and 0.25-fold the cl, respectively by default, controlled by the qMult and q2Mult arguments to pkncaControl

When both intravascular and extravascular doses are present (doses into the observation compartment are intravascular), ka is estimated from the extravascular doses and vc and cl are estimated from the intravascular doses; without extravascular-only doses, ka is not updated. Intravascular bolus doses have the concentration at the time of dosing back-extrapolated (replacing a predose concentration at the first dose), and other doses without a concentration at the time of dosing have it imputed as the predose concentration (or zero for the first dose).

The bounds for the parameter estimates are set to 10% of the first percentile and 10 times the 99th percentile. (For ka, the lower bound is set to the lower of 10% of the first percentile or 0.03 and the upper bound is not modified from 10 times the 99th percentile.)

Parameter estimation methods may be changed in a future version.