Using PBPK modelling and simulation in precision dosing in cirrhosis
Research type
Research Study
Full title
Utilising Physiologically Based Pharmacokinetic Modelling and Simulation for Precision Dosing in Cirrhotic Patients
IRAS ID
253207
Contact name
Eman Elkhateeb
Contact email
Sponsor organisation
University of Manchester
Duration of Study in the UK
3 years, 0 months, 30 days
Research summary
Cirrhosis is characterized by a loss in the functional liver mass leading to a disturbance not only in hepatic metabolism but also in all other pharmacokinetic parameters; absorption, distribution as well as excretion. Due to the lack of dosage recommendation in this specific patient population for a large number of already approved drugs, and the increasing demands for inclusion of hepatic impaired patients into early phases of clinical trials prior to drug approval, the need for highly qualified predictive tools like Physiologically Based Pharmacokinetics (PBPK) has become apparent. This project aims to improve the predictive ability of physiological cirrhosis models for dose adjustment with the following objectives:
-Assessment of drug metabolising enzymes and transporters in cirrhotic patients at different stages of the disease using liver samples collected from those patients for other purposes (Explant livers or tissues surrounding cancer).
-Investigation of the role of PBPK in dosage adjustment in patients with hepatic impairment and implications on clinical trial design.
-Modeling and simulation of a number of drugs using Simcyp® Simulator to satisfy the clinical needs in routine practice due to a shortage of labeling information in cirrhotic populations.REC name
London - London Bridge Research Ethics Committee
REC reference
18/LO/1969
Date of REC Opinion
5 Nov 2018
REC opinion
Favourable Opinion