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Some Considerations on the Design of Population Pharmacokinetic Studies

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Abstract

The goal of this manuscript is to introduce a framework for consideration of designs for population pharmacokinetic orpharmacokinetic–pharmacodynamic studies. A standard one compartment pharmacokinetic model with first-order input and elimination is considered. A series of theoretical designs are considered that explore the influence of optimizing the allocation of sampling times, allocating patients to elementary designs, consideration of sparse sampling and unbalanced designs and also the influence of single vs. multiple dose designs. It was found that what appears to be relatively sparse sampling (less blood samples per patient than the number of fixed effects parameters to estimate) can also be highly informative. Overall, it is evident that exploring the population design space can yield many parsimonious designs that are efficient for parameter estimation and that may not otherwise have been considered without the aid of optimal design theory

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References

  1. H.C. Kimko S.B. Duffull (2003) Simulation for Designing Clinical Trials Vol 127 Marcel Dekker New York

    Google Scholar 

  2. M.K. Al-Banna A.W. Kelman B. Whiting (1990) ArticleTitleExperimental design and efficient parameter estimation in population pharmacokinetics J. Pharmacokinet. Biopharm 18 347–360 Occurrence Handle10.1007/BF01062273 Occurrence Handle2231324 Occurrence Handle1:STN:280:By6D3sfnslY%3D

    Article  PubMed  CAS  Google Scholar 

  3. E.N. Jonsson J.R. Wade M.O. Karlsson (1996) ArticleTitleComparison of some practical sampling strategies for population pharmacokinetic studies J. Pharmacokinet Biopharm 24 245–263 Occurrence Handle8875349 Occurrence Handle1:STN:280:ByiD38bjtlM%3D

    PubMed  CAS  Google Scholar 

  4. F. Mentre A. Mallet D. Baccar (1997) ArticleTitleOptimal design in random-effects regression models Biometrika 84 IssueID2 429–442 Occurrence Handle10.1093/biomet/84.2.429

    Article  Google Scholar 

  5. S. Retout S. Duffull F. Mentre (2001) ArticleTitleDevelopment and implementation of the population Fisher information matrix for the evaluation of population pharmacokinetic designs Comput. Meth. Prog. Biomed 65 IssueID2 141–51 Occurrence Handle1:STN:280:DC%2BD3M7os12htA%3D%3D

    CAS  Google Scholar 

  6. S. Retout F. Mentre (2003) ArticleTitleFurther developments of the Fisher information matrix in nonlinear mixed effects models with evaluation in population pharmacokinetics J. Biopharm. Stat 13 209–227 Occurrence Handle10.1081/BIP-120019267 Occurrence Handle12729390

    Article  PubMed  Google Scholar 

  7. B. Green S.B. Duffull (2003) ArticleTitleProspective evaluation of a D-optimal designed population pharmacokinetic study J. Pharmacokinet. Pharmacodyn 30 IssueID2 145–161 Occurrence Handle10.1023/A:1024467714170 Occurrence Handle12942685 Occurrence Handle1:CAS:528:DC%2BD3sXms1yhtLs%3D

    Article  PubMed  CAS  Google Scholar 

  8. D.Z. D′Argenio (1981) ArticleTitleOptimal sampling times for pharmacokinetic experiments J. Pharmacokinet. Biopharm. 9 739–56 Occurrence Handle7341758 Occurrence Handle1:STN:280:Bi2C1M3htVc%3D

    PubMed  CAS  Google Scholar 

  9. A.C. Atkinson A.N. Donev (1992) Optimum Experimental Designs Clarendon Press Oxford

    Google Scholar 

  10. S. Retout F. Mentre (2003) ArticleTitleOptimization of individual and population designs using Splus J. Pharmacokinet. Pharmacodyn. 30 IssueID6 417–443 Occurrence Handle10.1023/B:JOPA.0000013000.59346.9a Occurrence Handle15000423

    Article  PubMed  Google Scholar 

  11. S.B. Duffull S. Retout F. Mentre (2002) ArticleTitleThe use of simulated annealing for finding optimal population designs Comput. Meth. Prog. Biomed 69 IssueID1 25–35

    Google Scholar 

  12. T. H. Waterhouse, S. Redman, S. B. Duffull, and J. A. Eccleston. Optimal design for model discrimination and parameter estimation for itraconazole population pharmacokinetics. J. Pharmacokinet. Pharmacodyn. (2005), In press.

  13. S.B. Duffull F. Mentre L. Aarons (2001) ArticleTitleOptimal design of a population pharmacodynamic experiment for ivabradine Pharm Res 18 IssueID1 83–89 Occurrence Handle10.1023/A:1011035028755 Occurrence Handle11336357 Occurrence Handle1:CAS:528:DC%2BD3MXjtFajt74%3D

    Article  PubMed  CAS  Google Scholar 

  14. D.Z. D′Argenio (1990) ArticleTitleIncorporating prior parameter uncertainty in the design of sampling schedules for pharmacokinetic parameter estimation experiments Math. Biosci 99 105–118 Occurrence Handle2134510 Occurrence Handle1:STN:280:By2C1MbntF0%3D

    PubMed  CAS  Google Scholar 

  15. M. Tod J.M. Rocchisani (1997) ArticleTitleComparison of ED, EID and API criteria for the robust optimization of sampling times in pharmacokinetics J. Pharmacokinet. Biopharm 25 515–537 Occurrence Handle9561492 Occurrence Handle1:CAS:528:DyaK1cXis1Ojsbw%3D

    PubMed  CAS  Google Scholar 

  16. T.H. Waterhouse J.A. Eccleston S.B. Duffull (2003) On optimal design for discrimination and estimation University of Queensland Brisbane

    Google Scholar 

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Authors and Affiliations

  1. School of Pharmacy, University of Queensland, Brisbane, 4072, Australia

    Stephen Duffull

  2. School of Physical Sciences, University of Queensland, Brisbane, 4072, Australia

    Tim Waterhouse & John Eccleston

Authors
  1. Stephen Duffull
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  2. Tim Waterhouse
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  3. John Eccleston
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Correspondence to Stephen Duffull.

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Duffull, S., Waterhouse, T. & Eccleston, J. Some Considerations on the Design of Population Pharmacokinetic Studies. J Pharmacokinet Pharmacodyn 32, 441–457 (2005). https://doi.org/10.1007/s10928-005-0034-2

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  • DOI: https://doi.org/10.1007/s10928-005-0034-2

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