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Methods and Applications of Statistics in Clinical Trials, Volume 2: Planning, Analysis, and Inferential Methods by N. Balakrishnan

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Chapter 27

Noncompartmental Analysis

Jürgen B. Bulitta and Nicholas H.G. Holford

27.1 Introduction

The objectives of noncompartmental analysis (NCA) are often assessing dose proportionality, showing bioequivalence, characterizing drug disposition, and obtaining initial estimates for pharmacokinetic models. Specific results and applications of NCA are as follows: (1) The area under the concentration-time curve (e.g. in plasma or serum) describes the extent of systemic drug exposure; the peak concentration and its timing indicate the rate of drug input (absorption), and (2) NCA provides estimates for clearance, volume of distribution, terminal half-life, mean residence time, and other quantities. Application 1 serves purely descriptive purposes and requires almost no assumptions. Importantly, application 2 does rely on several assumptions that are similar to the assumptions for compartmental modeling. Standard NCA requires frequent (blood) samples to estimate pharmacokinetic parameters reliably. Numerical integration is most commonly used for NCA after extravascular input. Fitting of disposition curves by a sum of exponential functions, for example, is the method of choice for intravenous bolus input.

NCA of an adequately designed clinical trial can provide robust estimates for extent of drug exposure and rate of absorption and other quantities. NCA estimates for clearance and volume of distribution rely on several assumptions that have to be critically considered for appropriate ...

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