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Abstract:
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Population pharmacokinetic (PPK) models are nonlinear mixed-effects models that describe the time-course of drugs in biological tissues (usually plasma or serum), and consist of the following component models: structural, inter-individual, covariate, and residual error models. PPK models were initially developed to describe observational concentration-time data, are now the method of choice to describe drug exposure in patients (as model parameters can be determined from sparsely sampled drug concentrations). PPK models are used to characterize the variability of drug exposures a target patient population, and thereby recommend dose adjustments based on subject covariates. Additionally, individual estimates of drug exposures determined by PPK models may be utilized to characterize exposure-response relationships of efficacy, safety, or biomarkers of drug effect. This presentation will describe conventional and simulation based graphical diagnostics of model performance, visualization of the effect of continuous and categorical covariates on structural model parameters, and comparisons of summary measures of drug exposure in subgroups of patients (conditional on their covariates).
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