Second Generation Sulfonylureas

The second-generation sulfonylureas display a higher specificity and affinity for the sulfonylurea receptor and more predictable pharmacokinetics in terms of time of onset and duration of action, and they have fewer side effects. Second-generation sulfonylureas may also exert mild diuretic effects on the kidney and are highly protein bound, primarily through nonionic binding (in contrast to the ionic binding observed with the first-generation compounds).

Glyburide (DiaBeta, Micronase, Glynase), also known as glibenclamide, is approximately 150 times as potent as tolbutamide on a molar basis and twice as potent as glipizide (discussed later). Glyburide is completely metabolized in the liver to two weakly active metabolites before excretion in the urine. Its average duration of action is 24 hours.

Glipizide (Glucotrol) is similar to glyburide, but it is metabolized by the liver to two inactive metabolites; these metabolites and glipizide are renally excreted.

Glimepiride (Amaryl) is metabolized to at least one active metabolite. It is quickly absorbed from the gastrointestinal tract within an hour of oral administration and excreted in the urine and feces. Its half-life varies from 5 to 9 hours depending on the frequency of multiple dosing.

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