title: Application of neural networks to population pharmacokinetic data analysis.
abstract: This research examined the applicability of using a neural network approach to analyze population pharmacokinetic data. Such data were collected retrospectively from pediatric patients who had received tobramycin for the treatment of bacterial infection. The information collected included patient-related demographic variables (age, weight, gender, and other underlying illness), the individual's dosing regimens (dose and dosing interval), time of blood drawn, and the resulting tobramycin concentration. Neural networks were trained with this information to capture the relationships between the plasma tobramycin levels and the following factors: patient-related demographic factors, dosing regimens, and time of blood drawn. The data were also analyzed using a standard population pharmacokinetic modeling program, NON-MEM. The observed vs predicted concentration relationships obtained from the neural network approach were similar to those from NONMEM. The residuals of the predictions from neural network analyses showed a positive correlation with that from NONMEM. Average absolute errors were 33.9 and 37.3% for neural networks and 39.9% for NONMEM. Average prediction errors were found to be 2.59 and -5.01% for neural networks and 17.7% for NONMEM. We concluded that neural networks were capable of capturing the relationships between plasma drug levels and patient-related prognostic factors from routinely collected sparse within-patient pharmacokinetic data. Neural networks can therefore be considered to have potential to become a useful analytical tool for population pharmacokinetic data analysis.
authors.affiliation: Department of Pharmacy Practice and Science, University of Arizona, Tucson 85721, USA.
authors.forename: H H
authors.initials: HH
authors.lastname: Chow
authors.forename: K M
authors.initials: KM
authors.lastname: Tolle
authors.forename: D J
authors.initials: DJ
authors.lastname: Roe
authors.forename: V
authors.initials: V
authors.lastname: Elsberry
authors.forename: H
authors.initials: H
authors.lastname: Chen
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001424:Bacterial Infections / Q000188:drug therapy; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D016571:Neural Networks, Computer; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D014031:Tobramycin / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D014031:Tobramycin