Pharmaceutical Statistics Using SAS

7.8. Pharmacokinetic Models with Multiple Measurements per Patient

In this section we discuss a clinical pharmacokinetic (PK) study where multiple blood samples are taken for each enrolled patient. This setup leads to nonlinear mixed effects regression models with multiple responses.

7.8.1. Two-Compartment Pharmacokinetic Model

Consider a clinical trial in which the drug was administered as a bolus input D₀ at the beginning of the study (at time x = 0) and then bolus inputs D_i were administered at 12 or 24 hour intervals until 72 hours after the first dose. To describe the concentration of drug at time x, a two-compartment model was used with standard parameterization (volume of distribution V, transfer rate constants K₁₂, K₂₁ and K₁₀), see ...