PopPK

Population pharmacokinetics (PopPK) is a branch of pharmacometrics that studies variability in drug pharmacokinetics across individuals in a target population and describes how covariates such as age, weight, organ function, genetics, and disease state affect PK parameters. PopPK uses mathematical models that describe drug concentration-time data across individuals and occasions, with the central objective of estimating typical population values for parameters like clearance, volume of distribution, and sometimes absorption rate, while quantifying and explaining inter-individual and residual variability.

Most PopPK analyses use nonlinear mixed-effects modeling to separate between-subject variability from within-subject variability, using random effects. Data are often sparse or irregular, and PopPK supports inference with limited samples per individual while helping to design dosing regimens. Structural models are typically compartmental (one-, two-, or multi-compartment), with statistical models for variability and covariate relationships.

Outputs include population parameter estimates, measures of variability, identified covariate relationships, and simulation tools to predict exposure under different doses or patient characteristics. Applications span dose individualization, pediatric and special-population dosing, dosing optimization in renal or hepatic impairment, and regulatory submissions. PopPK is routinely used in drug development and clinical practice to optimize efficacy and safety and to generalize dosing guidelines beyond a single patient.

Validation and diagnostics are integral, including goodness-of-fit plots, visual predictive checks, bootstrap, and external validation. Limitations include model misspecification, data quality issues, sparse covariates, and potential over-parameterization. PopPK complements PK/PD analyses to relate drug exposure to response and adverse effects.