Advanced search ?

Object

Download

Title: Prediction of pro-arrhythmic activity in humans with the use of physiologically based pharmacokinetics and pharmacodynamics modelling

Author:

Patel, Nikunjkumar

Date:

2018

Type:

Praca doktorska

Abstract:

Drug induced cardiac arrhythmia, especially occurrence of Torsade de Pointes (TdP), has been a leading cause of attrition and post-approval re-labelling and withdrawal of many drugs. TdP is a multifactorial event, reflecting more than just drug-induced cardiac ion channel inhibition and QT interval prolongation. A drug that is well tolerated in most patients can cause TdP in a particular individual under certain clinical situations e.g. co-medications or electrolyte imbalance. Moreover, assessment of the TdP liability of a drug based only on the parent moiety and the hERG centric evaluations could be misleading. Testing all probable hypotheses in clinical and/or animal studies may be practically, ethically and economically unfeasible. These present a translational gap in extrapolating preclinical cardiac safety assessment to estimate human TdP risk reliably. As part of this thesis, it was demonstrated with case examples how mechanistic approach such as Quantitative Systems Toxicology and Safety (QSTS) an be used from early discovery to late stage drug development and post marketing surveillance safety assessment where the model can be further verified, refined and enriched by “predict-learn-confirm” process as more in vitro and clinical data becomes available. Adoption of such QSTS modelling strategies can significantly benefit precise TdP risk assessment and mitigation.

Place of publishing:

Kraków

Level of degree:

2 - studia doktoranckie

Degree discipline:

choroby układu krążenia ; farmakologia

Degree grantor:

Wydział Farmaceutyczny

Promoter:

Polak, Sebastian ; Wiśniowska, Barbara

Date issued:

2018

Identifier:

oai:dl.cm-uj.krakow.pl:4471

Call number:

ZB-130305

Language:

eng; pol

Access rights:

nieograniczony

Subject and keywords:

mathematical modeling physiology based pharmacokinetic models drugs cardiotoxicity polypharmacy pharmacokinetics

Object collections:

Last modified:

Dec 30, 2024

In our library since:

Feb 2, 2022

Number of object content hits:

200

Number of object content views in PDF format

0

All available object's versions:

http://dl.cm-uj.krakow.pl:8080/publication/4472

Show description in RDF format:

RDF

Show description in OAI-PMH format:

OAI-PMH

Edition name Date
ZB-130305 Dec 30, 2024

Objects

Similar

Prediction of pro-arrhythmic activity in humans with the use of physiologically based pharmacokinetics and pharmacodynamics modelling

Patel, Nikunjkumar

2018
Praca doktorska

Effects of sepsis on the pharmacokinetics of selected drugs with different hepatic extraction ratios in mice

Przejczowska-Pomierny, Katarzyna

2022
Praca doktorska

Kącik farmakokinetyczny

materiały edukacyjne

Materiały dydaktyczne - Zakład Farmakologii Uniwersytetu Medycznego w Łodzi

materiały edukacyjne

Development and performance verification of the pharmacokinetic model towards determination of the active drug fraction surrogate in the heart tissue

Tylutki, Zofia

2018
Praca doktorska

Development and performance verification of the pharmacokinetic model towards determination of the active drug fraction surrogate in the heart tissue

Bielecka, Zofia

2018
Praca doktorska

Determination of ADME processes of new H3 receptor antagonist from the group of piperidine derivatives

Szafarz, Małgorzata

2012
Praca doktorska

Vancomycin in the treatment of infective endocarditis in patients in the postoperative period

Hońdo, Łukasz

2019
Praca doktorska
More
×

Citation

Citation style:

Contact details

Address

Medical Library
Medyczna 7
30-688 Krakow

Phone

12 658 72 56
517 385 669

E-Mail

Collecting and Elaboration Department
cyfrowabm@cm-uj.krakow.pl

Visit us!

This page uses 'cookies'. More information