Population Pharmacokinetic Analysis using PKBugs and WinBUGS

Authors:
Stephen Duffull, School of Pharmacy, University of Queensland, Brisbane, Australia.

Nick Holford, Department of Pharmacology and Clinical Pharmacology, University of Auckland, Auckland, New Zealand.

Carl Kirkpatrick, School of Pharmacy, University of Queensland, Brisbane, Australia.

Bruce Green, School of Pharmacy, University of Queensland, Brisbane, Australia.

 
The "fuzzy caterpillar"
 

"WinBUGS" for population pharmacokinetic analyses

The material presented on this site was originally developed by Stephen Duffull and Nick Holford for workshops run at the PAGANZ 2001 and the PAGE 2002  annual scientific meetings. The aim of this website is to assist new users with the practical application of PKBugs and WinBUGS for the analysis of population pharmacokinetics.   The instructions and data sets provided in the downloads area allow a step by step approach to illustrate this technique for population analysis.   Although the example provided is for a population pharmacokinetic analysis, this tool can equally be applied to pharmacodynamic analyses.  It is assumed that users will have a passing knowledge of Bayesian techniques.  If you require further readings on Bayesian techniques or Markov chain Monte Carlo (MCMC) methods please see the references section.

PKBugs is a pharmacokinetically orientated interface for WinBUGS that prompts the user for inputs and automatically generates the pseudo-code used by WinBUGS.   It will generate the necessary code, convert NONMEM compatible data files into the rectangular array format required, and sets up code for multiple dosing histories.  The link to software and manuals for PKBugs and WinBUGS is available from our links area below.  The software is currently available free.

The "wiggly snake"

Downloads

All the necessary files to get started are below.  You must first register, download, install and request the key for WinBUGS from the appropriate websites below.

Once you have done this, you can download the example:
1) download the instructions PDF
2) download the "zipped" data file (contains all the necessary "odc" files and data files).
[NB All files with the "odc" extension should be opened using WinBUGS, these are not ascii files.]

Instructions for using PKBUGS and WinBUGS with the example model and some numerical outputs from the BUGS runs

Data files .  A description of the files contained in the zip file is in the "instructions" file.  This also contains instructions on how to prepare your own files from a NONMEM datafile.

If you are unsure of what you are doing, watch the WinBugs Movie!.

Two chains

LINKS

PKBugs Website
WinBUGS Website
WinBugs Movie
Modeling and simulation group, School of Pharmacy, University of Queensland,
Pharmacometrics, University of Auckland

 Useful references

A non-technical introduction to the use of Markov chain Monte Carlo techniques

Jonsson F, Johanson G. The Bayesian population approach to physiological toxicokinetic-toxicodynamic models--an example using the MCSim software. Toxicol Lett. Feb 18 2003;138(1-2):143-150.

An more detailed introduction to MCMC for PK/PD analysis

Lunn DJ, Best N, Thomas A, Wakefield J, Spiegelhalter D. Bayesian analysis of population PK/PD models: general concepts and software. J Pharmacokinet Pharmacodyn. 2002;29(3):271-307.

Best NG, Tan KK, Gilks WR, Spiegelhalter DJ. Estimation of population pharmacokinetics using the Gibbs sampler. J Pharmacokinet Biopharm. Aug 1995;23(4):407-435.