bta, page-4

re: bta worrying signs A strain [isolate?] of the H5N1 avian influenza virus that may unleash the next global flu pandemic is showing resistance to Tamiflu, the antiviral drug that countries around the world are now stockpiling to fend off the looming threat. Experts in Hong Kong said on Friday [30 Sep 2005] that the human H5N1 strain [isolate?] which surfaced in northern Viet Nam this year had proved to be resistant to Tamiflu, a powerful antiviral drug.

They urged drug manufacturers to make more effective versions of Relenza, another antiviral that is also known to be effective in battling the much-feared H5N1. Relenza is inhaled [whereas Tamiflu is taken orally]. "There are now resistant H5N1 strains [isolates] appearing, and we can't totally rely on one drug (Tamiflu)," William Chui, honorary associate professor with the Department of Pharmacology at the Queen Mary Hospital in Hong Kong, told Reuters. Chui was referring to the Tamiflu-resistant strain of H5N1 [avian influenza] in Viet Nam. Chui also said general viral resistance to Tamiflu was growing in Japan, where doctors habitually prescribe the drug to fight common influenza.

Switzerland's Roche Holdings AG makes Tamiflu, known generically as oseltamivir, and GalaxoSmithKline makes Relenza, or zanamivir. "Manufacturers should think about producing an injectable form of Relenza because resistance to Tamiflu has been seen in Japan and Viet Nam. Also with injections, high doses can be given where necessary and onset time is a lot faster," Chui said.

Drugs that are administered intravenously can be better absorbed in patients who have stomach and acidity problems, another expert said. "We don't have to worry about absorption, injections take drugs right in. But if the patient takes them orally, maybe some amounts won't be absorbed or some may be destroyed by stomach acids," said pharmacist Raymond Mak at Queen Mary Hospital. Intravenous Relenza would also ensure faster onset, which would be critical in patients who are seriously ill. "Orally taken drugs take 3-4 hours to reach maximum blood concentration and 3-4 hours is very critical in severe cases. But injectable Relenza takes only 30 minutes to reach maximum blood concentration, this is a huge difference," Chui said. With an intravenous antiviral, doctors can also vary the doses.

While the H5N1 virus is now mostly passed directly from bird to human, health experts have warned that it is just a matter of time before it mutates into a form that is easily transmissible between people. When that happens, it may result in as many as 150 million human deaths.

2 reports in The Lancet this month said that resistance to anti-influenza drugs was growing worldwide. In places such as China, drug resistance exceeded 70 percent, suggesting that drugs like amantadine and rimantadine will probably no longer be effective for treatment or as a preventive in a pandemic outbreak of flu, the reports said.