Pharmacokinetic analysis of multi PEG-theophylline conjugates.

Mario Grassi, Gian Maria Bonora, Sara Drioli, Francesca Cateni, Marina Zacchigna

Department of Industrial Engineering and Information Technology, University of Trieste, Via Valerio 6/A, 34127 Trieste, Italy. mariog@dicamp.univ.trieste.it

Computational biology and chemistry 2012 Oct

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In the attempt of prolonging the effect of drugs, a new branched, high-molecular weight multimeric poly(ethylene glycol) (MultiPEG), synthesized with a simple assembling procedure that devised the introduction of functional groups with divergent and selective reactivity, was employed as drug carrier. In particular, the attention was focused on the study of theophylline (THEO) and THEO-MultiPEG conjugates pharmacokinetic after oral administration in rabbit. Pharmacokinetic behavior was studied according to an ad hoc developed mathematical model accounting for THEO-MultiPEG in vivo absorption and decomposition into drug (THEO) and carrier (MultiPEG). The branched high-molecular weight MultiPEG proved to be a reliable drug delivery system able to prolong theophylline staying in the blood after oral administration of a THEO-MultiPEG solution. The analysis of experimental data by means of the developed mathematical model revealed that the prolongation of THEO effect was essentially due to the low THEO-MultiPEG permeability in comparison to that of pure THEO. Copyright © 2012 Elsevier Ltd. All rights reserved.

Citation

Mario Grassi, Gian Maria Bonora, Sara Drioli, Francesca Cateni, Marina Zacchigna. Pharmacokinetic analysis of multi PEG-theophylline conjugates. Computational biology and chemistry. 2012 Oct;40:7-14