| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 15174 | Computational Biology and Chemistry | 2012 | 8 Pages |
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.
Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlight► Prolonged theophylline effect if administered as a multimeric PEG-drug solution. ► Reliable mathematical model for the PK data interpretation. ► Multimeric PEG-theophylline decomposition occurs after GI mucosa crossing. ► Prolonged theophylline effect is mainly due to conjugate permeability reduction.
