Imperial College London
Alternate

ProfessorRongjunChen

Faculty of Engineering, Department of Chemical Engineering

Professor of Biomaterials Engineering
 
 
 
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Contact

 

+44 (0)20 7594 2070rongjun.chen Website

 
 
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Location

 

408ACE ExtensionSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Gu:2019:10.3390/pharmaceutics11030111,
author = {Gu, B and Piebalgs, A and Huang, Y and Longstaff, C and Hughes, A and Chen, R and Thom, S and Xu, X},
doi = {10.3390/pharmaceutics11030111},
journal = {Pharmaceutics},
title = {Mathematical modelling of intravenous thrombolysis in acute ischaemic stroke: Effects of dose regimens on levels of fibrinolytic proteins and clot lysis time},
url = {http://dx.doi.org/10.3390/pharmaceutics11030111},
volume = {11},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Thrombolytic therapy is one of the medical procedures in the treatment of acute ischaemic stroke (AIS), whereby the tissue plasminogen activator (tPA) is intravenously administered to dissolve the obstructive blood clot. The treatment of AIS by thrombolysis can sometimes be ineffective and it can cause serious complications, such as intracranial haemorrhage (ICH). In this study, we propose an efficient mathematical modelling approach that can be used to evaluate the therapeutic efficacy and safety of thrombolysis in various clinically relevant scenarios. Our model combines the pharmacokinetics and pharmacodynamics of tPA with local clot lysis dynamics. By varying the drug dose, bolus-infusion delay time, and bolus-infusion ratio, with the FDA approved dosing protocol serving as a reference, we have used the model to simulate 13 dose regimens. Simulation results are compared for temporal concentrations of fibrinolytic proteins in plasma and the time that is taken to achieve recanalisation. Our results show that high infusion rates can cause the rapid degradation of plasma fibrinogen, indicative of increased risk for ICH, but they do not necessarily lead to fast recanalisation. In addition, a bolus-infusion delay results in an immediate drop in plasma tPA concentration, which prolongs the time to achieve recanalisation. Therefore, an optimal administration regimen should be sought by keeping the tPA level sufficiently high throughout the treatment and maximising the lysis rate while also limiting the degradation of fibrinogen in systemic plasma. This can be achieved through model-based optimisation in the future.
AU  - Gu,B
AU  - Piebalgs,A
AU  - Huang,Y
AU  - Longstaff,C
AU  - Hughes,A
AU  - Chen,R
AU  - Thom,S
AU  - Xu,X
DO  - 10.3390/pharmaceutics11030111
PY  - 2019///
SN  - 1999-4923
TI  - Mathematical modelling of intravenous thrombolysis in acute ischaemic stroke: Effects of dose regimens on levels of fibrinolytic proteins and clot lysis time
T2  - Pharmaceutics
UR  - http://dx.doi.org/10.3390/pharmaceutics11030111
UR  - http://hdl.handle.net/10044/1/68656
VL  - 11
ER  -
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