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Short of Tamiflu

Aside from the question whether antiviral drugs like Tamiflu are of much use for combating a future influenza pandemic (avian flu or bird flu), there is additionally a severe shortage of the drugs. Present stocks only cover about 2% of the population of the world. Furthermore, shortage of raw materials (Star anise in the case of Tamiflu) makes it very difficult to increase production over current levels.

Doubling the stockpile

However, a gout drug called Probenecid (brand names Benemid, Probalan) is able to extend the effective duration of many a drug's presence (as well as the presence of alcohol) in the patient's bloodstream, by some 2.5 times. In this way the patient would only need to take less than half of the normal dose of Tamiflu (and of similar influenza drugs), thereby effectively doubling the present Tamiflu stockpile in the world. The same method would of course also double the world stockpile of Jack Daniel's and of Beefeater.

Probenecid is a rather simple chemical, a derivative of benzoic acid. In gout prevention Probenecid works by increasing the kidneysā€™ ability to remove uric acid from the blood -- it's crystals of uric acid that precipitate in the joints (particularly in the toes) and cause the gout symptoms.

On the other hand, by preferentially making the kidneys remove uric acid, other substances in the blood are removed less efficiently. They linger on in the bloodstream for a much longer time than usual. In addition, the initial peak concentration of the substance is much higher than when Probenecid is not present.

Safely lowering the cost of penicillin ā€“- and of alcohol

The substances that Probenecid prevents the kidneys from removing from the bloodstream include alcohol, anti-inflammatory drugs (e.g. ibuprofen), antibiotics (including penicillin), aspirin, and -- a whole series of antiviral drugs, including oseltamivir (Tamiflu).

Tamiflu manufacturer Roche found this out already in 2002, and published the data. However, there has been no interest to put this finding to any practical use, not by Roche, nor by the health authorities. In a recent article in Nature, Joe Howton, a medical director in Portland, Oregon, expressed surprise and dismay at this lack of interest. Probenecid was used during WW II to help extend scarce supplies of penicillin and there is plenty of data showing that Probenecid is a safe drug.

Combinationally unsafe?

However, to my mind, the safety of Probenecid in itself is hardly sufficient for proving that the combination of Probenecid and Tamiflu is safe. All antiviral influenza drugs, including Tamiflu, have side effects, some of them serious. By prolonging their time in the bloodstream you prolong the side effects as well. In the case of Jack Daniel's it would double your hangover. Before jumping to conclusions, extensive clinical testing is certainly called for.

Last straw hysteria

The main question is of course not how to make the stocks of rather inefficient antiviral drugs last longer, but whether antiviral influenza drugs are at all capable of dealing with a possible outbreak of a new influenza pandemic. And here the answer appears to be negative (see Influenza drugs and Tamiflu). The Tamiflu discussion seems to have blown out of all proportion into a hysterical "last straw bubble", fuelled by the media-fanned public bird flu scare.

Reference:

G. Hill et al. Drug Metab. Dispos. 30, 13-19; 2002
http://www.nature.com/news/2005/051031/full/438006a.html
http://www.drugdigest.org/DD/DVH/Uses/0,3915,562%7CProbenecid,00.html
http://fluwikie.com

Thanks to N0b0dY, who alerted me to this development.

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