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Unsupervised learning of pharmacokinetic responses

Author

Listed:
  • Elson Tomás

    (Universidade de Lisboa)

  • Susana Vinga

    (Universidade de Lisboa)

  • Alexandra M. Carvalho

    (Universidade de Lisboa)

Abstract

Pharmacokinetics (PK) is a branch of pharmacology dedicated to the study of the time course of drug concentrations, from absorption to excretion from the body. PK dynamic models are often based on homogeneous, multi-compartment assumptions, which allow to identify the PK parameters and further predict the time evolution of drug concentration for a given subject. One key characteristic of these time series is their high variability among patients, which may hamper their correct stratification. In the present work, we address this variability by estimating the PK parameters and simultaneously clustering the corresponding subjects using the time series. We propose an expectation maximization algorithm that clusters subjects based on their PK drug responses, in an unsupervised way, collapsing clusters that are closer than a given threshold. Experimental results show that the proposed algorithm converges fast and leads to meaningful results in synthetic and real scenarios.

Suggested Citation

  • Elson Tomás & Susana Vinga & Alexandra M. Carvalho, 2017. "Unsupervised learning of pharmacokinetic responses," Computational Statistics, Springer, vol. 32(2), pages 409-428, June.
    • Handle: RePEc:spr:compst:v:32:y:2017:i:2:d:10.1007_s00180-016-0707-x
    DOI: 10.1007/s00180-016-0707-x
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    References listed on IDEAS

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    4. Kuhn, E. & Lavielle, M., 2005. "Maximum likelihood estimation in nonlinear mixed effects models," Computational Statistics & Data Analysis, Elsevier, vol. 49(4), pages 1020-1038, June.
    5. Wu L., 2002. "A Joint Model for Nonlinear Mixed-Effects Models With Censoring and Covariates Measured With Error, With Application to AIDS Studies," Journal of the American Statistical Association, American Statistical Association, vol. 97, pages 955-964, December.
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