How cystic fibrosis modulator drugs move and work in the human body

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1. Please give a summary of your research.

Brief Summary:Cystic fibrosis is a life limiting disease caused by defective or deficient cystic fibrosis trans-membrane conductance regulator activity. The recent approval of lumacaftor combined with ivacaftor targets 70% of CF patients with F508del-CFTR. Unfortunately, the clinical efficacy of these important drugs is limited by our limited understanding of the way these drugs move (pharmacokinetics, PK) and work (pharmacodynamics, PD) in the human body. This innovative project will investigate the PK-PD of these drugs in patients from multiple CF centres world-wide and has significant potential in improving clinical practice worldwide.

Impact: My research program directly addresses cystic fibrosis (CF) which is the most common, genetically acquired, life-shortening chronic illness affecting young Australians today. There is no cure, and patients with CF undergo life-long and extremely costly medical treatments. In the last couple of years, I have intensively worked on the pharmacology of two new breakthrough CF medications. I am now able to provide an analytical therapeutic drug monitoring platform for clinicians to improve patients’ outcomes by optimization of therapy. The outcomes of my research have improved the lives of the ~3,500 registered CF patients in Australia. 

Project Aim: The overall Aim of this innovative project will provide the first-ever PK/PD and pharmacology data to support more efficacious CFTR corrector therapy for life threatening CF. The Specific Aims are to: (1) To conduct a multi-centre pharmacokinetic study of ivacaftor and lumacaftor using CF patient plasma samples. (2) To optimize dosage regimens of ivacaftor and lumacaftor using patient PK data and PK/PD modeling.

This project has clear translational potential and provides a solid foundation for clinical trials in future.

2. Please include any additional details you would like to share

I am a passionate pharmacist whose long-term career goal is to propel innovations in medical discovery, development and deliver in respiratory diseases. My long term career aspiration seeks to build on my track record in cystic fibrosis and establish an independent group. Through regular conference participation, I myself have extended my international network to more than 10 Cystic fibrosis centres world-wide through meeting and establishing collaborations with clinicians. My aim is to visit all the CF centres and implement my therapeutic monitoring platform to improve patients’ outcomes by optimising therapy.

Conducting a multi-centre PK study of ivacaftor/lumacaftor using CF patient samples will determine the PK and the data will inform the PK/PD study (Aim 2). The most predictive PK/PD index and target values will be identified for the cystic fibrosis modulator drugs, and the optimal dosage regimens will be obtained. My work will provide the first-ever PK/PD and pharmacology data to support more efficacious CFTR corrector therapy for life threatening CF. This multi-disciplinary proposal will provide the first scientifically based recommendations for optimized dosage regimens for ivacaftor and lumacaftor for improved therapeutic outcomes for CF patients.


Adil Hanif
over 1 year ago

Seems like a ery innovative project. Wonderful

Tatiana Ascencio
over 1 year ago