AAPS PharmSci

, Volume 1, Issue 4, pp 5–13 | Cite as

Empirical versus mechanistic modelling: Comparison of an artificial neural network to a mechanistically based model for quantitative structure pharmacokinetic relationships of a homologous series of barbiturates

  • Ivan NestorovEmail author
  • Malcolm Rowland
  • S. T. Hadjitodorov
  • I. Petrov


The aim of the current study was to compare the predictive performance of a mechanistically based model and an empirical artificial neural network (ANN) model to describe the relationship between the tissue-to-unbound plasma concentration ratios (Kpu's) of 14 rat tissues and the lipophilicity (LogP) of a series of nine 5-n-alkyl-5-ethyl barbituric acids. The mechanistic model comprised the water content, binding capacity, number of the binding sites, and binding association constant of each tissue. A backpropagation ANN with 2 hidden layers (33 neurons in the first layer, 9 neurons in the second) was used for the comparison. The network was trained by an algorithm with adaptive momentum and learning rate, programmed using the ANN Toolbox of MATLAB. The predictive performance of both models was evaluated using a leave-one-out procedure and computation of both the mean prediction error (ME, showing the prediction bias) and the mean squared prediction error (MSE, showing the prediction accuracy). The ME of the mechanistic model was 18% (range, 20 to 57%), indicating a tendency for overprediction; the MSE is 32% (range, 6 to 104%). The ANN had almost no bias: the ME was 2% (range, 36 to 64%) and had greater precision than the mechanistic model, MSE 18% (range, 4 to 70%). Generally, neither model appeared to be a significantly better predictor of the Kpu's in the rat.


Artificial Neural Network Hide Layer Artificial Neural Network Model Predictive Performance PBPK Model 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© American Association of Pharmaceutical Scientists 1999

Authors and Affiliations

  • Ivan Nestorov
    • 1
    Email author
  • Malcolm Rowland
    • 1
  • S. T. Hadjitodorov
    • 2
  • I. Petrov
    • 2
  1. 1.Centre for Applied Pharmacokinetic Research, School of Pharmacy and Pharmaceutical SciencesUniversity of ManchesterManchesterUK
  2. 2.Centre for Biomedical EngineeringBulgarian Academy of SciencesSofiaBulgaria

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