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Tolazamide appears to lower the blood glucose acutely by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets. The mechanism by which tolazamide lowers blood glucose during long-term administration has not been clearly established. With chronic administration in Type II diabetic patients, the blood glucose lowering effect persists despite a gradual decline in the insulin secretory response to the drug. Extrapancreatic effects may be involved in the mechanism of action of oral sulfonylurea hypoglycemic drugs.
Some patients who are initially responsive to oral hypoglycemic drugs, including TOLINASE (tolazamide) Tablets, may become unresponsive or poorly responsive over time. Alternatively, TOLINASE (tolazamide) Tablets may be effective in some patients who have become unresponsive to one or more other sulfonylurea drugs.
Tolazamide is rapidly and well absorbed from the gastrointestinal tract. Peak serum concentrations occur at three to four hours following a single oral dose of the drug. The average biological half-life of the drug is seven hours. The drug does not continue to accumulate in the blood after the first four to six doses are administered. A steady or equilibrium state is reached during which the peak and nadir values do not change from day to day after the fourth to sixth doses.
Tolazamide is metabolized to five major metab-olites ranging in hypoglycemic activity from 0-70%. They are excreted principally in the urine. Following a single oral dose of tritiated tolazamide, 85% of the dose was excreted in the urine and 7% in the feces over a five-day period. Most of the urinary excretion of the drug occurred within the first 24 hours post administration.
When normal fasting nondiabetic subjects are given a single 500 mg dose of tolazamide orally, a hypoglycemic effect can be noted within 20 minutes after ingestion with a peak hypoglycemic effect occurring in two to four hours. Following a single oral dose of 500 mg tolazamide, a statistically significant hypoglycemic effect was demonstrated in fasted nondiabetic subjects 20 hours after administration. With fasting diabetic patients, the peak hypoglycemic effect occurs at four to six hours. The duration of maximal hypoglycemic effect in fed diabetic patients is about ten hours, with the onset occurring at four to six hours and with the blood glucose levels beginning to rise at 14 to 16 hours. Single dose potency of tolazamide in normal subjects has been shown to be 6.7 times that of tolbu-tamide on a milligram basis. Clinical experience in diabetic patients has demonstrated tolazamide to be approximately five times more potent than tolbu-tamide on a milligram basis, and approximately equivalent in milligram potency to chlorpropamide.
Last reviewed on RxList: 12/8/2004
This monograph has been modified to include the generic and brand name in many instances.
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