Gout drug might cut AZT dosage by half.

Gout drug might cut AZT dosage by half

A drug developed in the 1940s to keep penicillin in the blood longer may do the same for zidovudine (AZT), the only drug approved to treat AIDS. Researchers report that probenecid reduces zidovudine inactivation and excretion -- boosting blood levels between doses an average of 80 percent compared with zidovudine alone.

Though the trial included only eight patients, it indicates probenecid, now used to treat gout, could halve the daily dose of zidovudine without changing overall effectiveness, says study director David M. Kornhauser of the Johns Hopkins University School of Medicine in Baltimore. If so, such a change could essentially halve the cost of treatment, he says.

The total cost nationally of zidovudine therapy -- estimated at $8,000 annually per patient -- might skyrocket if each of the estimated 1.5 million Americans infected with HIV, the AIDS-causing virus, received zidovudine. Two recent studies indicate the drug delays the onset of AIDS (SN: 8/26/89, p. 135).

Kornhauser and his co-workers gave probenecid and zidovudine to eight AIDS or AIDS-related-complex patients. Fearing probenecid might work too well -- increasing zidovudine's toxic effects as well as its anti-HIV activity -- they first reduced each patient's zidovudine dose. Zidovudine levels rose in every patient, but in varying amounts -- from 14 percent to 192 percent, the team reports in the Aug. 26 LANCET. The researchers saw no increase in side effects or adverse changes in symptoms.

Kornhauser says no researcher would recommend changes in clinical practice after studying only eight patients, but "a large-scale trial looking at the combination of AZT and probenecid would be reasonable if you think of the health costs to the nation as a whole."

AIDS patients often require several medications. Because probenecid is known to increase levels of many drugs, Kornhauser suggests testing it early in the HIV infection, before patients require medications other than zidovudine.

Margaret Lynn Smiley, medical adviser for the department of antimicrobial therapy at Burroughs Wellcome Co. of Research Triangle Park, N.C. -- maker of zidovudine -- remains concerned about probenecid's effects on other drugs. She says even asymptomatic patients in the near future won't get zidovudine alone. "This [probenecid] is just a way of maximizing one antiviral, but now we're looking at combination therapies," she says. "In future AIDS anti-viral therapy there are going to be drugs targeted toward different enzymes or different parts of the viral replication cycle."