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Clinical pharmacology studies conducted at Newcastle have led to optimisation of the administration of the chemotherapy drug carboplatin in children with neuroblastoma and other cancers. The research provided the rationale for carboplatin dosing based on patient renal function, with individualised dosing resulting in increased drug efficacy and reduced toxicity. This approach is now in widespread use in national and European treatment protocols, benefitting over 2,500 children. Similar drug monitoring approaches are being implemented for an increasing number of important drugs. Following a recent Newcastle-led national clinical trial, new dosing guidelines for the drug 13-cis retinoic acid have been adopted for high-risk neuroblastoma patients across Europe.
Research led by Professor Brown has led to widespread changes in clinical practice regarding the management of Hypertension. Following his demonstration that patients' response to drugs for Hypertension is variable (in a systematic manner), subsequent clinical guidelines acknowledged the variability among patients, and changed from recommending the same treatment for all patients, to an algorithm based on the Cambridge AB/CD rule. The simplicity of the AB/CD rule led to popularity among doctors, and adoption by national bodies — British Hypertension Society, NICE, and foreign guidelines, and by textbooks of Medicine. The guidelines arising from his research have contributed to improved health outcomes in the UK. Specifically, NICE's simple and rational guidance how to reach strict targets for blood pressure is credited with changing the UK from the poorest to best performing country in Europe.
A routine test to screen for patients genetically disposed to serious side effects from treatment with thiopurine drugs has been widely adopted following research by the Academic Unit of Clinical Pharmacology at the University of Sheffield. The test has spared patients painful and potentially life-threatening sepsis, and saved the considerable associated treatment costs which have been estimated to be over £9,000 per patient for a 17 day hospital stay. It has also led directly to a change in clinical guidelines and recommendations in both the USA and UK.
Warfarin is an anti-coagulant drug prescribed to tens of millions of people in the UK and US who are at high risk of developing blood clots. Because individual sensitivity to warfarin varies in the population there is a risk of overdosing the drug and causing serious bleeding and even stroke in many people when starting treatment. In 1999 researchers at Newcastle University were the first to demonstrate a statistically significant link between a person's genotype and the appropriate dose of warfarin. In 2010 the US Food and Drug Administration (FDA) mandated inclusion of a table of dose recommendations based on genotype in the warfarin prescribing information leaflet accompanying the drug. Newcastle research forms the basis of the 2009 international standard algorithm for gene-guided dosing of warfarin. This approach has been adopted by large US medical centres and the FDA states that it will prevent 17,000 strokes a year in the US.
Research at the University of Sheffield contributed to the development by GlaxoSmithKline (GSK) of a drug to treat Irritable Bowel Syndrome (IBS) that has transformed the lives of thousands of patients and generated significant revenue. The drug, alosetron, which blocks 5-HT3 receptors in the gastrointestinal tract, was approved by the Food and Drug Administration (US) (FDA) in 2000 and launched under the trade name Lotronex. It is currently the only drug on the market aimed specifically at the treatment of diarrheal IBS. Although GSK voluntarily withdrew the drug from the market following concerns over possible side effects, Lotronex was relaunched in 2004 following petition from IBS sufferers and user groups. The licence for Lotronex was sold in 2008 to Prometheus Laboratories, Inc. and annual sales of the drug now exceed $34 million. In 2011 Prometheus was bought by Nestle for an estimated $1.1billion. This case study has significant impact on commerce and health and welfare.
Research from Professor Tom Brown's group in Chemistry at Southampton has made a major contribution towards tackling the issue of ineffective drug therapies using Scorpion Primer Technology. Originally commercialised through DxS Ltd., the major impacts derived since 2008 include:
The university's Pharmacy and Pharmacology unit has developed and validated novel in silico and in vitro/ex vivo models for use by the pharma industry to select drug candidates, optimise formulations, determine the posology for clinical trials and show bioequivalence. This resulted in: the approval of two products for actinic keratosis (Picato® and Zyclara®); a generic nail formulation approved for use based on the demonstration of equivalence using the in vitro/ex vivo models described with no clinical testing (the first time this has occurred); and the translation and commercialisation of two dermal drug delivery-based patented technologies (licensing deals with Sinclair IS and major pharmaceutical companies).
Labelled compounds form an essential part of drug discovery and development within the pharmaceutical industry. Novel iridium catalysts, developed by Kerr at WestCHEM since 2008, have introduced a step-change in the ability to label pharmaceutical candidate compounds with radioactive (tritium) or non-radioactive (deuterium) isotopes.
The catalysts are applicable to specific types of compounds that comprise approximately one-third of all drug candidates. Advantages of the catalysts include greater efficacy (less catalyst needed and higher yield of labelled product, giving cost savings), greater speed (efficiency savings), and a significant decrease in radioactive waste compared with previous methods (environmental and safety benefits).
Even since 2008, their adoption within the pharmaceutical industry has been extremely rapid; e.g., the multinational pharmaceutical company AstraZeneca now applies the Kerr methodology to 90% of their relevant candidate compounds. Additional impact has been achieved by Strem Chemicals who have been manufacturing and marketing the catalysts worldwide since October 2012. Even in that very short period, multiple sales have been made on three continents providing economic benefit to the company.
Research by Professor Abdul Basit's group at the UCL School of Pharmacy is leading to improved treatments for ulcerative colitis and other conditions through increased knowledge of the complex physiology of the gastrointestinal tract. Improved understanding of in vivo drug release and uptake has allowed development of three patent-protected technologies for improved drug delivery: PHLORALTM, for release of drugs in the colon, and DuoCoatTM and ProReleaseTM formulations designed to allow intact transit through the stomach followed by immediate release upon gastric emptying. These technologies are the subject of licences and ongoing development programmes, with PHLORALTM currently in phase III clinical trials. The impact is therefore the introduction of enabling technologies that have positively influenced the drug development programmes of pharmaceutical companies.
Research at the University of Sheffield developed pharmacokinetic tools that enable prediction of drug absorption, distribution, metabolism and excretion, and potential drug-drug interactions. In 2001 the University created a spinout company, Simcyp Ltd, to commercialise the technology. The impacts are: