Effects of pyrazinamide, probenecid, and benzbromarone on renal excretion of oxypurinol

Article Abstract:

The effects of allopurinol, a medication used to control production of uric acid in patients with gout, are chiefly due to oxypurinol, its major metabolite (breakdown product). After conversion of allopurinol to oxypurinol, the metabolite is excreted by the kidney without further reactions. The concentration of oxypurinol in blood must reach certain levels in order to be therapeutically effective, as is true for most drugs, and the blood level of oxypurinol is directly rated to the rate of removal of the drug from the blood by the kidneys. The kidney appears to handle oxypurinol similarly to uric acid, but this has not been well studied. Probenecid and benzbromarone are two drugs which are used to treat gout, as they increase kidney excretion of uric acid. These seem to inhibit kidney reabsorption (removal from urine back into the tissues and circulation) of uric acid at a distant portion of kidney tubules, after tubular secretion (secretion of solutes or salts back into the tubular fluid that becomes urine). The effects of these two drugs and that of pyrazinamide, an antitubercular drug which inhibits tubular secretion of uric acid, on renal (kidney) excretion of oxypurinol was studied in 15 healthy men. Pyrazinamide decreased renal clearance of oxypurinol by over half, but had no effect on the drug's blood levels. Probenecid increased renal clearance of oxypurinol by almost half, and benzbromarone had a similar effect. Neither of these last two drugs affected blood levels of oxypurinol. The results suggest that oxypurinol is indeed reabsorbed from urine into kidney tissues after secretion of solutes into the urine-containing tubule. The study suggests that in combination therapy using allopurinol and benzbromarone, the effects together may be less than would be expected from their single effects on uric acid metabolism. (Consumer Summary produced by Reliance Medical Information, Inc.)

Kidneys, Kidney, Drug interactions, Allopurinol

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Increased concentrations of serum Lp(a) lipoprotein in patients with primary gout

Article Abstract:

Lipoprotein levels tend to be increased among gout patients, which is a risk factor for cardiovascular disease. Cardiovascular disease is more common among gout patients. Concentrations may be decreased by taking niceritorol without exacerbating the gout. Serum lipoprotein was measured among 175 men with gout and compared with values from 172 non-gouty men. Gout patients had an average lipoprotein value of 15.5 milligrams per decaliter versus 8.6 milligrams per decaliter among healthy control subjects. Gout patients were more likely to have values in the upper range and less likely to have values in the lower range. Fifteen gout patients with high lipoprotein concentrations were given moderate dosages of niceritorol, and blood serum evaluations one, three, and five months later showed reduced lipoprotein levels without an increase in serum uric acid. High doses of niceritorol have been shown to be effective but serum uric acid levels increase.

Risk factors, Atherosclerosis, Lipoproteins, Blood lipoproteins

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Apolipoprotein E phenotypes in patients with gout: relation with hypertriglyceridaemia

Article Abstract:

The apolipoprotein e4 gene may be more prevalent among gout patients with high levels of fat in the blood, or hyperlipidemia, than in people with normal levels of fat in the blood. Researchers compared blood samples taken after fasting of 221 male gout patients with 141 men who did not have gout. They found that although the apolipoprotein (apo) E gene type was identified in similar numbers of people with gout and without, the apo E4/3 gene type was found more often in hyperlipidemic patients with gout. Gout patients with the apo E4/3 gene type had higher blood levels of triglyceride and cholesterol than did gout patients with the apo E3/3 gene type. This finding suggests that the apo e4 gene fragment may play a role in increasing blood levels of fat in gout patients.

Research, Abnormalities, Apolipoproteins, Hyperlipidemia, Disease susceptibility, Lipid metabolism disorders, Lipidosis

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