nlmixr: an R package for population PKPD modeling

nlmixr

nlmixr is an R package for fitting general dynamic models, pharmacokinetic (PK) models and pharmacokinetic-pharmacodynamic (PKPD) models in particular, with either individual data or population data. The nlme and SAEM estimation routines can be accessed using a universal user interface (UUI), that provides universal model and parameter definition syntax and results in a fit object that can be used as input into the Xpose package. Running nlmixr using the UUI is described in the vignette: https://github.com/nlmixrdevelopment/nlmixr/blob/master/vignettes/running_nlmixr.Rmd

Under the hood nlmixr has five main modules:

  1. dynmodel() and its mcmc cousin dynmodel.mcmc() for nonlinear dynamic models of individual data;
  2. nlme_lin_cmpt()for one to three linear compartment models of population data with first order absorption, or i.v. bolus, or i.v. infusion using the nlme algorithm;
  3. nlme_ode() for general dynamic models defined by ordinary differential equations (ODEs) of population data using the nlme algorithm;
  4. saem_fit for general dynamic models defined by ordinary differential equations (ODEs) of population data by the Stochastic Approximation Expectation-Maximization (SAEM) algorithm;
  5. gnlmm for generalized non-linear mixed-models (possibly defined by ordinary differential equations) of population data by the adaptive Gaussian quadrature algorithm.

A few utilities to facilitate population model building are also included in nlmixr.

For a brief vignette describing the modules, please see: https://github.com/nlmixrdevelopment/nlmixr/blob/master/inst/nlmixr-intro.pdf

The examples in the vignette can be run using VignetteDemo.R and the associated data files available at: https://github.com/nlmixrdevelopment/nlmixr/tree/master/vignettes

For PKPD modeling (with ODE and dosing history) with Stan, check out Yuan’s package PMXStan:

Installation

You can install the released version of nlmixr from CRAN with:

And the development version from GitHub with:

# install.packages("devtools")
devtools::install_github("nlmixrdevelopment/nlmixr")

Example