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Thursday 22 June 2006

Administration of usual therapeutic doses of gemfibrozil considerably increases the plasma concentrations of rosiglitazone 10-fold, an insulin-sensitizing drug used to treat patients with Type 2 diabetes mellitus


Gemfibrozil, a lipid-lowering agent, was recently demonstrated to dangerously increase the plasma concentrations of another antidiabetic drug, repaglinide. Because fibrates are commonly used to lower triglyceride levels in diabetics, M. Niemi and colleagues of the Helsinki University Central Hospital in Finland, investigated a possible interaction between gemfibrozil and rosiglitazone.

The investigators performed a randomized, placebo-controlled crossover study in which 10 healthy volunteers (9 men, 1 woman) took 600 mg gemfibrozil or placebo orally twice daily for 4 days, and a single 4 mg dose of rosiglitazone on day 3.

Day 3 food intake was standardized, and patients received food at 3 hours and 7 hours after rosiglitazone administration. Venous blood samples were collected before and for up to 48 hours after rosiglitazone administration.

Gemfibrozil was found to raise the mean area under the plasma rosiglitazone concentration-time curve 2.3-fold, as well as increase the elimination half-life from 3.6 to 7.6 hours. Additionally, while gemfibrozil had only a minor effect on peak plasma rosiglitazone concentration (a 1.2-fold increase), the plasma rosiglitazone concentration measured at 24 hours post administration increased almost 10-fold.

Considerable variability between individuals in the extent of drug interaction was noted, with the relative increase in rosiglitazone concentration ranged from 51 to 179%.

Concomitant administration of the two drugs may enhance rosiglitazone efficacy, but may also increase the risk of concentration-dependent adverse effects. "Due to the possibility of an increased risk of adverse effects, it could be advisable to avoid co administration of gemfibrozil and rosiglitazone," researchers say.

The researchers recommend that rosiglitazone dose be reduced by about 50 to 70% if gemfibrozil treatment is started on a patient using rosiglitazone, and the patient carefully monitored for signs and symptoms of adverse effects. Diabetologia 2003 Jul 29

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