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Certara research sheds light on drug resistant influenza

Certara, a specialist in model-informed drug development has announced that it has developed a report on viral kinetic (VK) modelling to accelerate research into drug-resistant strains of influenza. The review has just been published in Current Pharmacology Reports.

As the number of drug-resistant influenza strains grows, and the challenge to identify the best strains to include in the next year’s vaccine continues, researchers are searching for better ways to develop safer, more effective anti-viral drugs. ‘This paper describes how mathematical models, and especially viral kinetic models, can increase researchers’ knowledge of influenza biology and antiviral pharmacology,’ said co-author Professor Carl Kirkpatrick, director of the Centre of Medicine Use and Safety (CMUS) at Monash University, Melbourne, Australia.

‘For example, population-based viral kinetic models can identify sources of variation between and within individuals, helping to explain why some influenza patients become sicker than others,’ said Professor Kirkpatrick.

Underscoring the impact of this disease, the United States Centers for Disease Control and Prevention estimates that influenza has resulted in between 9.2 million and 35.6 million illnesses, between 140,000 and 710,000 hospitalisations, and 12,000-56,000 deaths annually since 2010.

These Viral kinetic models have been used to support the dose optimisation of neuraminidase inhibitors and also the clinical development of monoclonal antibodies that are currently being investigated as potential influenza therapies.

Viral kinetic models use mathematical equations to describe the changes in viral load with time in an infected patient. They can provide valuable information about the cell infection rate, viral production rate, and viral clearance rate.

‘By combining viral kinetic models with PK/PD models, researchers can quantify drug effects based on their mechanism of action and evaluate in silico the efficacy of specific drug combinations. Together, these models can be used to explore how antiviral drugs reduce influenza symptoms and viral load,’ said Lead author and Certara executive director, consulting services Mark Lovern, PhD.

‘PK/PD models are also starting to be coupled to epidemiological and health economic models to assess the effectiveness of public health treatment strategies. Epidemiologic models can quantify changes in susceptible, exposed, infected, and recovered patients during an outbreak and assess the ease with which an infectious disease can be transmitted among them,’ said Suzanne Minton, PhD, Certara scientific communications manager and co-author.

‘Health economic models then determine the relative change in quality-adjusted life-years based on the predicted number of infected patients. We anticipate that this ‘pharmacology to payer’ framework will inform decisions regarding managing existing and emerging pathogens on a global scale,’ added Patrick Smith, PharmD, chief scientific officer at Certara Strategic Consulting Services and co-author. ‘They can be employed to justify drug costs to payers and also to determine the likely transmission patterns for pandemic infectious diseases, helping to optimise the use of stockpiled national medical resources.’

The paper, which is titled: ‘Applications of Influenza Viral Kinetic Modeling in Drug Development,’ can be found at https://link.springer.com/article/10.1007/s40495-017-0104-3.

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