PKPDmallit

PKPDmallit is a modular framework and software tool designed to support pharmacokinetic and pharmacodynamic modeling and simulation. It provides an integrated environment for building, fitting, and evaluating PK/PD models to inform dose selection and trial design. The name suggests its focus on linking concentration-time data (PK) with response-time data (PD).

Core components include: a data manager, a declarative model specification language, an estimation engine that supports frequentist and Bayesian methods, diagnostics tools, and a simulation module. The framework is designed to accommodate common structural models such as one- and two-compartment pharmacokinetic models with first- or zero-order absorption, as well as nonlinear clearance and time-varying covariates. PD models include Emax, sigmoidal Emax, indirect response models, and simple exposure–response relationships. PK/PD linkage is achieved through effect compartments or direct linkage by concentration.

Estimation options typically cover maximum likelihood estimation and Bayesian inference via MCMC, with support for prior information and parallel computation. Workflows usually involve data import, model specification, covariate modeling, selection of estimation method, model diagnostics (residuals, visual predictive checks), and extensive simulations to predict exposure and response under alternative dosing regimens.

Applications include dose optimization, scenario analysis for trial design, and regulatory submissions. Output consists of parameter estimates with uncertainty, goodness-of-fit diagnostics, and simulation-based plots. Limitations include the need for statistical and pharmacometric expertise and computational resources, as well as the risk of model misspecification. PKPDmallit is presented as an evolving concept in pharmacometrics, intended to complement existing tools rather than replace them.