Pharmaceutics Research

Role of P-glycoprotein (Pgp) and interleukin-2 (IL-2) in liver transplant Patients.

Investigators: Dr Romina Nand and Dr Andrew McLachlan.

This may be a 6 month prospective study where we can look at P-glycoprotein expression and interleukin-2 levels in blood from liver transplant patients and correlate with clinical outcome (rejection status). Would also be good to follow some patients who are waiting for a liver transplant. IL-2 levels can be measured by the IL-2 assay or flow cytometry. Pgp can also be measured using the Pgp assay or flow cytometry. Maybe possible to simultaneously measure IL-2 and Pgp using flow cytometry.



Hepatic disposition of tacrolimus using the isolated perfused rat liver model.

Investigators: Dr Romina Nand, Dr Iqbal Ramzan and Dr Andrew McLachlan.

In this study, we can explore the effects of protein binding (albumin and AAG) and drug interaction on the bioavailability of tacrolimus. This study may be used to emphasise the importance of unbound tacrolimus concentration as the key determinant of clinical outcome. We can also further explore drug interaction studies. This study will make use of the the IPRL cabinet.



Effect of alpha1-acid glycoprrotein on the hepatic disposition of quinidine.

Investigators: Dr Romina Nand, Dr Iqbal Ramzan and Dr Andrew McLachlan

This project will investigate in more detail the role of AAG on the hepatic uptake of quinidine. This will be continuation of my PhD project.



In Vitro

Investigator: Dr Iqbal Ramzan

Anti-Cholinesterase Activity of Newer Proton Pump Inhibitors.

Effect of Lipid Lowering Drugs on Plasma Cholinesterase Activity.

Pulmonary Metabolism of Fluticasone Propionate (FP).

Uptake of drugs by the prostate.



In Vivo-Animal

Investigator: Dr Iqbal Ramzan

Examination of the hepatic first pass effect of quaternary ammonium compounds including tacrine and pyridostigmine.

First pass effect of the inhaled corticosteroids (with Dr Andrew McLachlan)

First pass effect of model peptides and proteins studied using the isolated perfused rat liver (IPRL) preparation.



In Vivo- Patients

Investigator: Dr Iqbal Ramzan

Use of neuromuscular blockers as pharmacokinetic and /or pharmacodynamic probes of graft liver function during liver transplantation surgery.

Propofol pharmacodynamics: determinants of variability.



Dispersion of Dry Powders as Aerosols for Inhalation

Investigators: Dr Nora Chew, Ravindra Behara, Praveen Maharaj and Dr Kim Chan

Overall objective: To investigate the physico-chemical determinants for dispersion of pharmaceutical powders as aerosols suitable for delivery to human airways. Specific aims are to:

- explore powder surface properties for enhanced generation of fine particles (0.5 - 5 µm) in the aerosol
- determine suitable operating conditions to maximise aerosolisation efficiency
- establish the relationship between the powder properties and operating conditions in optimising aerosol performance.

Significance: Pharmaceutical inhalation products or aerosols such as the chlorofluorocarbon (CFC) propellent-driven metered dose inhalers are used widely to deliver drugs to the lung for local effect (eg asthma). As a result of the adverse environmental impact of CFC propellants, there is an urgent need to develop alternative methods of generation of therapeutic aerosols. Aerosols generated from fine dry powders are among the most promising substitutes for CFC devices for inhalation use. Dry powder aerosols are less likely to suffer from physical instability and chemical incompatibility problems, they are inherently simpler to use and they have a lower potential for toxic effects than devices that require propellants. Furthermore, there is increasing interest in using the inhalation route for the delivery of new types of drugs such as proteins and genes for systemic effects (eg using the lung to deliver insulin to the bloodstream for diabetics). Preparation of proteins as dry powder aerosols has been shown to be a very promising approach to deliver the drugs to the respiratory tract.



Novel Aerosol Inhaler by Thermal Ink Jet Technology

Investigators: Dr Nora Chew and Dr Kim Chan

Overall objective: to develop a novel technology for safe, reliable and economical production of fine aerosol particles for drug delivery to the lung.

Significance: Because of the shortcomings in currently available drug delivery systems, there is intense interest in creating alternative technologies. Aerosol based systems are among the most promising. An aerosol system based on mechanical extrusion of liquid is currently in advanced stages of clinical trial in the USA. Another prototype has been developed based on piezo-electric principles. We believe that the thermal liquid jet technology has considerable potential because:

Of the possibility of changing the liquid jet nozzles and thereby allowing varying particle sizes and doses, and also allowing different mixes of drugs in one dose.
Of high reliability as there are no moving parts.
The anticipated finished product will be disposable and of low cost by using commercial off the shelf components.


Projects

• The distribution and disposition of immunosuppressant and other drugs in transplant recipients (Dr Andrew McLachlan, Dr Romina Nand and Prof Geogh McCaughan)
• Drug interactions in transplant recipients (Dr Andrew McLachlan, Dr Romina Nand and Prof Geogh McCaughan)
• Physiologically-based pharmacokinetic models to describe and predict tissues concentrations of drugs (Dr Andrew McLachlan and Dr Mahboubeh Hosseini)
• Population pharmacokinetic investigations in special subgroups of patients including children with malignant disease, transplant recipients, people with HIV infection and patients with rheumatoid arthritis (Dr Andrew McLachlan)
  Renal drug handling (Dr Andrew McLachlan, Prof Susan Tett and Dr Annette Gross)
• Drug disposition and metabolism in the isolated perfused liver preparation (Dr Iqbal Ramzan, Dr Andrew McLachlan)
• Microdialysis as a tool for assessing peripheral pharmacokinetics (Dr Andrew McLachlan and Dr Iqbal Ramzan)
• Interaction between herbal medicines and warfarin (Dr Andrew McLachlan and A/Prof K Williams)
• Population Pharmacokinetics of anti-cancer drugs (Dr Andrew McLachlan, Dr Laurent Rivory and Dr Stephen Clarke)
• Therapeutic drug monitoring of anti-retroviral drugs (Dr Andrew McLachlan and Mr John Ray)