Diagnostics & Imaging Week Contributing Writer

LONDON – The era of personalized drug therapy is inching closer, but the investigations to determine which is the best drug is likely to include a urine test, as well as your genotype.

Researchers in Europe have shown that it is possible to predict an animal's response to a drug from the metabolic "signature" of its urine. The scientists' preliminary investigations on people suggest that human urine, too, holds hitherto untold information about how drugs are metabolised in individuals, based on their intrinsic metabolic profiles.

Jeremy Nicholson, professor of biological chemistry at Imperial College London told Diagnostic & Imaging Week's sister publication BioWorld International: "We have shown a proof of principle that a urinary metabolite profile has the potential to predict whether or not you are likely to have good or bad effects from drugs. If this approach can be fully developed, urine tests of this kind could be used on a huge scale to predict drug metabolism and drug fate, and possibly many other things about a person's health."

The same method could help predict how people will respond to a change in their diet, or even to events such as dealing with a bacterial infection.

"It's potentially applicable to every area of human and even animal medicine," Nicholson added. "It's a completely new way of looking at personalized health care for the future – a new way of screening people."

Nicholson has been working on metabolic profiling for the past 25 years. He calls the approach "pharmaco-metabonomics" to distinguish it from pharmacogenomics.

The latter is the study of how genomic variations affect the ways in which a drug is metabolized, and whether it is toxic. For example, there are some well-known polymorphisms in genes encoding enzymes that influence how well people can metabolize certain types of drugs. People who cannot metabolize these drugs well may suffer toxic side effects.

But genetic influences on drug metabolism can be very complex, and they are only part of the story. "Pharmacogenomics cannot capture the environmental element," Nicholson said.

The environment includes, for example, the millions of microbes that live on and in humans. Many have enzymes that can metabolize drugs, and they dose the human body with drug-like secondary metabolites, which switch human enzymes on and off. Earlier work by Nicholson's group showed that changing gut microbes caused drug metabolism to change, too.

To address these issues, Nicholson and his team decided to focus on the animal's metabolic profile, as seen in the urine, using nuclear magnetic resonance (NMR) spectroscopy. The strategy involves analyzing the NMR spectra of urine before and after an animal is given a drug, and using the pre-dose metabolic signature to predict the outcome of the drug dose.

Experiments carried out by the group demonstrated that the strategy can work. In one experiment, the researchers conducted NMR spectroscopy on urine samples from 10 rats. They then gave the animals galactosamine. It is a natural metabolite, not a drug, but given in large doses, some rats will suffer liver damage.

Among the 10 rats, six animals developed liver damage and four didn't. Analysis of the pattern of the NMR spectra showed that the animals that fell sick all had a similar type of NMR pattern, while those that remained healthy had a different NMR pattern.

A second experiment involved dosing rats with paracetamol at a level that sometimes causes liver damage. The researchers analyzed the pre-dose NMR patterns of the animals' urine, gave the drug, and then asked a histopathologist to score the level of liver damage.

That approach provided them with numerical values for both the NMR spectra, and the degree of liver damage. "You build a mathematical model that connects all the variables from the NMR spectra – the signature – to the outcome data on drug metabolism and drug toxicity," Nicholson said. "We found we could take the urine and predict, in a quantitative way, the metabolic fate of the drug and the quantitative level of liver damage."

The experiments are reported in the April 20, 2006, issue of Nature in a paper titled "Pharmaco-metabonomic phenotyping and personalized drug treatment."

Nicholson said preliminary tests using human urine, aimed at predicting the quantitative metabolism of paracetamol have had "very interesting" results.

"It looks as if we will be able to apply it to paracetamol," he said. "Future work will aim to find out how many different drug classes can be predicted in this way."

Welch Allyn builds on Asian 'hub'

Welch Allyn (Skaneateles Falls, New York) reported that it has acquired Malaysian medical products distributor MediAids – a move that will give the company said will give it "critical mass within a centralized Asian hub and complement its existing research and development facility in Singapore."

The company said the operation will allow it to utilize and expand on its core technologies to offer medical products that are specific to the needs of frontline caregivers in Asia and other emerging markets throughout the region.

"MediAids has been a strong Welch Allyn distributor for more than 20 years," said Con Hickey, vice president, Asia Pacific at Welch Allyn. "This acquisition provides us with a tremendous opportunity to build on the many years of success MediAids has had selling our products in Malaysia."

Welch Allyn's new Malaysian operation will enhance its' Singapore-based research and development facility established in 2004 to focus on the development of next generation technology for patient vital signs monitoring and advanced wireless technologies. The company currently has four other research and development facilities located across North America and Europe, and has received four Medical Design Excellence Awards and three R&D 100 Awards for its advanced product designs in recent years.

"Southeast Asia is undergoing a healthcare revolution," added Hickey. "The Malaysian government has signaled further investment in the refurbishment and expansion of hospitals and poly-clinics in the coming years, and private hospital investments provide a very real growth opportunity for us.

The new Welch Allyn Malaysia facility will remain at its current location and will be refurbished and modernized over time, the company said.

Calypte completes trial in South Africa

Calypte Biomedical (Lake Oswego) reported completing clinical studies in South Africa permitting the company to initiate sales of its Aware HIV-1/2 Oral Fluid (OMT) rapid test product in that country. This is a new approval for OMT in addition to the company's already approved blood test.

Studies conducted by the University of KwaZulu-Natal (Durban, South Africa) on the Aware HIV-1/2 OMT rapid test for oral fluid specimens showed sensitivity of 99.62% and specificity of 100% for a total of 600 subjects attending voluntary counseling and testing services in two Durban municipality clinics. The National Institute for Communicable Diseases (NICD) has issued a statement noting "that the design and execution of the study is in keeping with the standard approach used by the NICD reference lab to assess HIV-1/2 rapid kits for evaluation as part of the National Department of Health tender procedures." Therefore, "the results of the study are in keeping with the defined limits of acceptability and as such [the test] can be considered for tender purposes."

Roger Gale, CEO and chairman of Calypte, commented: "The conclusion of this clinical study allows the Company to market oral fluid rapid tests within the private markets in South Africa and to participate in government tenders as they are announced. AIS's 22 years of serving the South African clinical markets makes them an ideal partner to introduce Calypte's new non-invasive HIV-1/2 oral fluid test that we believe is ideally suited for the South African market."

Calypte said it believes that a non-invasive HIV-1/2 rapid test is ideal for the fight against AIDS in South Africa.

Cholestech LDX in 'Test the Nation' program

Cholestech (Hayward, California) reported that Flora pro.activ (London), the UK's leading cholesterol-lowering brand, has selected the Cholestech LDX System, a cholesterol monitoring tool, as part of the "Test the Nation" program. Cholestech said that this is the second national heart health initiative that has used the LDX System as the Swiss Heart Foundation recently submitted results of its national screening program to the Swiss Health Ministry.

"Test the Nation" is being run by Flora pro.activ, in association with H.E.A.R.T. UK, the Hyperlipidaemia Education and Research Trust, to provide information that will encourage people to find out what shape their heart is in. The campaign kicked off at the start of April and takes place at city centers, supermarkets and major events.

The cholesterol screening will be conducted using the LDX System, which generates lab-accurate results in minutes. Using a simple finger-stick, the LDX System can measure cholesterol, glucose and liver enzymes, and now, high sensitivity C-reactive protein (hs-CRP).

The Cholestech LDX System, carrying the CE mark, has been certified by the U.S. Cholesterol Reference Method Laboratory Network for the measurement of total cholesterol and HDL cholesterol consistent with National Cholesterol Education Program analytical goals.