Name
Title | ||
|---|---|---|
Compartmental modelling of the pharmacokinetics of a breast cancer resistance protein |
Abstract | ||
|---|---|---|
A mathematical model for the pharmacokinetics of Hoechst 33342 following administration into a culture medium containing a population of transfected cells (HEK293 hBCRP) with a potent breast cancer resistance protein inhibitor, Fumitremorgin C (FTC), present is described. FTC is reported to almost completely annul resistance mediated by BCRP in vitro. This non-linear compartmental model has seven macroscopic sub-units, with 14 rate parameters. It describes the relationship between the concentration of Hoechst 33342 and FTC, initially spiked in the medium, and the observed change in fluorescence due to Hoechst 33342 binding to DNA. Structural identifiability analysis has been performed using two methods, one based on the similarity transformation/exhaustive modelling approach and the other based on the differential algebra approach. The analyses demonstrated that all models derived are uniquely identifiable for the experiments/observations available. A kinetic modelling software package, namely FACSIMILE (MPCA Software, UK), was used for parameter fitting and to obtain numerical solutions for the system equations. Model fits gave very good agreement with in vitro data provided by AstraZeneca across a variety of experimental scenarios. |
Year | DOI | Venue |
|---|---|---|
2011 | 10.1016/j.cmpb.2010.08.018 | Computer Methods and Programs in Biomedicine |
Keywords | Field | DocType |
culture medium,compartmental modelling,exhaustive modelling approach,model fit,differential algebra approach,mathematical model,breast cancer resistance protein,vitro data,annul resistance,potent breast cancer resistance,kinetic modelling software package,non-linear compartmental model,dna structure,differential algebra,similarity transformation,kinetics | Drug Kinetics,Population,Abcg2,Fumitremorgin C,Biological system,Computer science,Identifiability analysis,Pharmacokinetics,In vitro,Bioinformatics,Statistics | Journal |
Volume | Issue | ISSN |
104 | 2 | 1872-7565 |
Citations | PageRank | References |
1 | 0.39 | 2 |
Authors | ||
6 | ||
Name | Order | Citations | PageRank |
|---|---|---|---|
| Thomas R. B. Grandjean | 1 | 3 | 1.46 |
| Mike J. Chappell | 2 | 1 | 0.39 |
| James W.T. Yates | 3 | 29 | 6.15 |
| Kevin Jones | 4 | 1 | 0.39 |
| Gemma Wood | 5 | 1 | 0.39 |
| Tanya Coleman | 6 | 1 | 0.39 |