Estimation of population pharmacokinetics using the Gibbs sampler |
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Authors: | Nicola G Best Keith K C Tan Wally R Gilks David J Spiegelhalter |
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Institution: | (1) Medical Research Council, Biostatistics Unit, Institute of Public Health, Robinson Way, Cambridge, UK;(2) Clinical Pharmacology Unit, University of Cambridge Clinical School, Addenbrooke's Hospital, Cambridge, UK;(3) Present address: Pfizer Central Research, Sandwich, Kent, UK |
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Abstract: | Quantification of the average and interindividual variation in pharmacokinetic behavior within the patient population is an
important aspect of drug development. Population pharmacokinetic models typically involve large numbers of parameters related
nonlinearly to sparse, observational data, which creates difficulties for conventional methods of analysis. The nonlinear
mixed-effects method implemented in the computer program NONMEM is a widely used approach to the estimation of population
parameters. However, the method relies on somewhat restrictive modeling assumptions to enable efficient parameter estimation.
In this paper we describe a Bayesian approach to population pharmacokinetic analysis which used a technique known as Gibbs
sampling to simulate values for each model parameter. We provide details of how to implement the method in the context of
population pharmacokinetic analysis, and illustrate this via an application to gentamicin population pharmacokinetics in neonates.
A grant from the British Heart Foundation supported Nicola G. Best. |
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Keywords: | Gibbs sampling population pharmacokinetics gentamicin |
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