TY - JOUR

T1 - Non-compartmental estimation of pharmacokinetic parameters for flexible sampling designs

AU - Jaki, Thomas

AU - Wolfsegger, Martin J.

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

KW - area under the concentration time curve

KW - AUC

KW - non-compartmental

KW - PK parameters

KW - sparse sampling

U2 - 10.1002/sim.4386

DO - 10.1002/sim.4386

M3 - Journal article

VL - 31

SP - 1059

EP - 1073

JO - Statistics in Medicine

JF - Statistics in Medicine

SN - 1097-0258

IS - 11-12

ER -