Understanding the influence of vitamin K on warfarin dosing requirements
My research projects are motivated by occurrence of a poorly understood phenomena termed transient warfarin resistance (TWR) – unexpectedly prolonged resistance to warfarin during warfarin reintroduction due to exogenously administered vitamin K. The overarching goal of my research is to obtain a better understanding of vitamin K and its relationship to the pharmacodynamic effects of warfarin.
To this end, the required steps include:
1. Quantifying the influence of warfarin on the time course of vitamin K-dependent clotting factors and anticoagulation proteins;
2. Determining sensitivity of international normalized ratio (INR) to changes in the quantity of clotting factor(s) by simulation;
3. Investigating conditions under which TWR can be resulted using a previously published comprehensive model for the humoral coagulation network in humans;
4. Developing a mechanism-based model for the coagulation kinetics and INR of warfarinised patients following administration of exogenously administered vitamin K.
Understanding azathioprine metabolism using a systems pharmacology approach
The overarching aim of this work is to develop dosing guidelines to improve safety and efficacy of azathioprine in the treatment of inflammatory bowel disease (IBD) by using modelling and simulation. The specific objectives of this work are :
- to describe the metabolite fate of azathioprine using a systems pharmacology model and
- to understand how differences in enzymatic activity affects the production of therapeutically active metabolites.”
Dose Individualisation of Dabigatran
Various scales have been developed to quantify anticholinergic burden, but they do not take into account the binding affinity of anticholinergic medicines to the muscarinic receptors. These tools incorrectly assume that the antimuscarinic effect is the same for all the medicines. Hence, our research aims to develop a dose-response based pharmacological tool to quantify anticholinergic burden that takes into account the binding of medicines to the muscarinic receptor.
To develop a full kinetic model for GPCRs
My PhD project aims to provide a complete description of the mathematical framework of GPCRs with an application to cannabinoid type 1 receptors (CB1Rs). The framework can be used to quantify the time course of effects of CB1 modulation on cAMP. This project will have generality to other GPCRs and ligands.
Exploring metrics for body composition
This work will explore available scaling metrics that are based on fat free mass, total body weight and surface area and account for altered body composition in people of different age groups. My research is focussed on developing a new fat free mass based size metric which will account for the age dependent body composition changes in children to elderly and can accurately estimate the paediatric dose.