Optimal intravenous bolus-infusion drug-dosage regimen based on two-compartment pharmacokinetic models

Kwang Seok Kim, Laurent Simon

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

An orthogonal collocation on finite elements-based regression method was applied to help design optimal drug-dosage regimens. The approach, suitable for two-compartment models, would allow clinicians to design multiple boluses followed by a constant-rate infusion of a medicament to patients in order to assure a desired plasma concentration. The algorithm was tested on theophylline, a drug that has been described by both linear and Michaelis-Menten elimination pharmacokinetics. In the linear case, increasing the number of boluses, from 1 to 4, decreased the normalized square root of the integral square error from 1.80 to 0.58 when a target concentration of 10 μg/mL was selected in the central compartment. When applied to the nonlinear metabolism, the procedure, implemented in Mathematica® (Wolfram Research, Inc.), effectively computed optimal dose sizes, injection times and infusion rates. Estimations, based on linear interpolation, provided a good time-saving alternative to the full optimization methodology.

Original languageEnglish (US)
Pages (from-to)1212-1219
Number of pages8
JournalComputers and Chemical Engineering
Volume33
Issue number6
DOIs
StatePublished - Jun 16 2009

All Science Journal Classification (ASJC) codes

  • Chemical Engineering(all)
  • Computer Science Applications

Keywords

  • Compartment model
  • Michaelis-Menten
  • Optimization
  • Pharmacokinetics
  • Theophylline

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