Clinical application of artificial neural network (ANN) modeling to predict pharmacokinetic parameters of severely ill patients.

Artificial neural network (ANN) modeling was used to evaluate the pharmacokinetics of aminoglycosides (arbekacin sulfate and amikacin sulfate) in severely ill patients. The plasma level was predicted by ANN modeling using parameters related to the severity of the patient's condition and the predictive performance was shown to be better than could be achieved using multiple regression analysis. These results indicate that there is a non-linear relationship between the pharmacokinetics of aminoglycosides and the severity of the patient's condition, and this should be taken into account when determining the dose for severely ill patients. Patients whose plasma levels are likely to fall below the effective level can be identified by ANN modeling with a predictive sensitivity and specificity superior to multivariate logistic regression analysis. The predictable range should be inferred from the data structure before the modeling in order to improve the predictive performance. The volume of distribution (Vd) in the normal range was weakly predicted by ANN modeling from the patients' data. Prediction of clearance by ANN modeling was poorer than that obtained from serum creatinine concentration by linear regression analysis. These results suggest that the input-output relationship (linear or non-linear) should be taken into account in selecting the modeling method. Linear modeling can give better predictive performance for linear systems and non-linear modeling can give better predictive performance for non-linear systems. In general, the performance of ANN modeling was superior to linear modeling for PK/PD prediction. For accurate modeling, a predictable range should be inferred from the data structure before the analysis. Restriction of the predictable region, as determined from the data structure, produced an increase in prediction performance. When applying ANN modeling in clinical settings, the predictive performance and predictable region should be investigated in detail to avoid the risk of harm to severely ill patients.