How is a sulfonylurea selected and how is it administered therapeutically

The choice is based on the potency, the dosage (see Table 27.1), the method of metabolism and the probability of causing undesirable side effects. Benefits from their usage, apart from control of blood sugar, that differentiate the second generation sulfonylureas from each other, are discussed below.

Sulfonylureas should be administered 20 minutes before meals, since they achieve drastic levels in the blood circulation one hour after their absorption by the peptic system. In any case, during chronic use, this characteristic is weakened. According to some researchers, the absorption of glibenclamide is not influenced by the intake of food, and that of glipizide is delayed by 90 minutes if it is received with the meal. Their plasma levels are decreased in conditions of hyperglycaemia, perhaps because of the deceleration of stomach emptying. Depending on each substance's half-life, they are administered once (glimepiride) or twice daily (gliclazide, glibenclamide). A recent study supports administration of glibenclamide once a day. Newer products of modified release are administered once a day (gliclazide modified release). The result of the administration depends on the dose of the medicine.

Sulfonylureas are transported in the plasma bound to albumin at > 90 percent. The half-life of second generation sulfonylureas varies (glibenclamide 3-5 hours, gliclazide 8-12 hours, glipizide 2.5-5 hours, glimepiride 5-8 hours). They are metabolized in the liver (which is why they should not be administered to individuals with hepatic insufficiency) and are excreted through urine or stools (glibenclamide by 50 percent from the kidneys, 50 percent by stools, glipizide and gliclazide 70 percent from the kidneys and roughly 10 percent by the stools, glimepiride 58 percent and 35 percent, respectively).

Patients with impaired renal function or the elderly should avoid treatment with sulfonylureas of longer duration of action. Glibenclamide, the most frequently prescribed sulfonylurea, can have a total duration of hypoglycaemic action of 24 hours, since its metabolites maintain their potency at 25 percent that of the full compound and can cause prolonged hypoglycaemias. A similar duration of action has also been reported for gliclazide, the metabolites of which are, however, inactive (as are those of glipizide, which has a shorter duration of action). Glimepiride also has a long duration of action.

Despite its long duration of action, glimepiride does not manifest a significant difference in the pharmacokinetic behaviour between younger and older patients, and does not accumulate in patients with disturbed renal function.

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