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

Document Type

Article

Publication Date

6-16-2009

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. © 2008 Elsevier Ltd. All rights reserved.

Identifier

65049092086 (Scopus)

Publication Title

Computers and Chemical Engineering

External Full Text Location

https://doi.org/10.1016/j.compchemeng.2008.12.001

ISSN

00981354

First Page

1212

Last Page

1219

Issue

6

Volume

33

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