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Non-compartmental estimation of pharmacokinetic parameters for flexible sampling designs


  • This report is an independent research arising from Dr. Jaki's Career Development Fellowship (NIHR-CDF-2010-03-32) supported by the National Institute for Health Research. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health.


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. Copycenter © 2011 John Wiley & Sons, Ltd.