getPPKinits: Automated pipeline for generating initial estimates in...

In nlmixr2autoinit: Automatic Generation of Initial Estimates for Population Pharmacokinetic Modeling

Automated pipeline for generating initial estimates in population PK models

Description

Provides a unified and fully automated workflow to generate initial pharmacokinetic and residual variability parameters for population PK models using concentration–time data from bolus, infusion, or oral administration.

Usage

getPPKinits(dat, control = initsControl(), verbose = TRUE)

Arguments

dat	A data frame containing pharmacokinetic records in standard nlmixr2 format, including ID, TIME, EVID, and DV.
control	A list created by initsControl() specifying configuration for pooling, non-compartmental analysis, steady-state detection, fallback rules, statistical model components, and parameter selection metrics.
verbose	Logical (default = TRUE); when TRUE, displays key progress messages and stepwise updates during the initialization process. When FALSE, the function runs quietly without printing intermediate information.

Details

The pipeline integrates four model-informed analytical components applied to raw or pooled concentration–time profiles:

1. Adaptive single-point methods

2. Naive pooled graphic methods

3. Naive pooled non-compartmental analysis (NCA) with optional Wagner–Nelson Ka calculation for oral dosing

4. Parameter sweeping across one-, two-, three-compartment and Michaelis–Menten models

In addition to structural PK parameters, the framework also initializes statistical model components:

• Inter-individual variability (IIV): pragmatic fixed \omega^2 values are assigned to random effects.

• Residual unexplained variability (RUV): estimated either using a data-driven method based on trimmed residual summaries or a fixed-fraction approach consistent with NONMEM User Guide recommendations.

• Model applicability: the automated and model-informed strategy generates robust initial values suitable for both linear and nonlinear mixed-effects pharmacokinetic models.

Value

An object of class getPPKinits containing recommended initial parameter estimates, intermediate results, and computation diagnostics.

Author(s)

Zhonghui Huang

See Also

initsControl, run_single_point, run_graphcal, run_pooled_nca, sim_sens_1cmpt_mm, sim_sens_2cmpt, sim_sens_3cmpt, metrics.

Examples

## Bolus example
getPPKinits(Bolus_1CPT,verbose = TRUE)
## Oral example (run quietly)
getPPKinits(Oral_1CPT,verbose = FALSE)

nlmixr2autoinit documentation built on Nov. 14, 2025, 1:07 a.m.