Individual dose-response models for levodopa infusion dose optimization

Int J Med Inform. 2018 Apr:112:137-142. doi: 10.1016/j.ijmedinf.2018.01.018. Epub 2018 Feb 1.

Abstract

Background and objective: To achieve optimal effect with continuous infusion treatment in Parkinson's disease (PD), the individual doses (morning dose and continuous infusion rate) are titrated by trained medical personnel. This study describes an algorithmic method to derive optimized dosing suggestions for infusion treatment of PD, by fitting individual dose-response models. The feasibility of the proposed method was investigated using patient chart data.

Methods: Patient records were collected at Uppsala University hospital which provided dosing information and dose-response evaluations. Mathematical optimization was used to fit individual patient models using the records' information, by minimizing an objective function. The individual models were passed to a dose optimization algorithm, which derived an optimized dosing suggestion for each patient model.

Results: Using data from a single day's admission the algorithm showed great ability to fit appropriate individual patient models and derive optimized doses. The infusion rate dosing suggestions had 0.88 correlation and 10% absolute mean relative error compared to the optimal doses as determined by the hospital's treating team. The morning dose suggestions were consistency lower that the optimal morning doses, which could be attributed to different dosing strategies and/or lack of on-off evaluations in the morning.

Conclusion: The proposed method showed promise and could be applied in clinical practice, to provide the hospital personnel with additional information when making dose adjustment decisions.

Keywords: Algorithmic dosing suggestions; Levodopa infusion; Parkinson’s disease; Patient-specific models.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms*
  • Antiparkinson Agents / administration & dosage*
  • Antiparkinson Agents / pharmacokinetics
  • Computer Simulation
  • Dose-Response Relationship, Drug
  • Female
  • Hospitalization / statistics & numerical data*
  • Humans
  • Infusions, Parenteral
  • Levodopa / administration & dosage*
  • Levodopa / pharmacokinetics
  • Male
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / metabolism
  • Tissue Distribution

Substances

  • Antiparkinson Agents
  • Levodopa