Non-compartmental estimation of pharmacokinetic parameters for flexible sampling designs

Pharmacokinetic (PK) studies aim to understand the kinetics of absorption, distribution, metabolism and elimination of a drug. Typically, such studies involve measuring the concentration of the drug in the plasma or blood at several time points after drug administration. In studying the PK behaviour, either the non-compartmental approach or alternatively a modelling approach can be utilized. Traditionally, the non-compartmental approach makes minimal assumptions about the data-generating process but requires the data to be collected in a very structured way. Conversely, the modelling approach depends heavily on assumptions about the data-generating process but does not impose a specific data structure. In this paper, we will discuss non-compartmental methods for estimating the area under the concentration versus time curve and other common PK parameters that use minimal assumptions about the data structure making it applicable to a wide range of PK studies. We will evaluate the methods using simulation and give an illustrative example.