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Clinical pharmacokinetics of sulfonylureas: a brief review.

All sulfonylureas seem to have similar mechanisms of action. Nevertheless, they may differ in their clinical effects because of differences in their pharmacokinetics and intrinsic activities. Second generation sulfonylureas, such as glibenclamide and glipizide, are much more potent than first generation sulfonylureas, such as tolbutamide and chlorpropamide. The former are, in fact, active at concentrations of the order of nmol/l, while the latter are active in the range of mumol/l. Accordingly, glibenclamide and glipizide are more efficient, and probably also less prone to cause pharmacokinetic interactions with other drugs, and with ethanol. In addition, glipizide and glibenclamide (new formulations) are completely bioavailable, which is a further advantage. Glipizide has a more rapid absorption and onset of action as well as a shorter half-life and duration of effect than glibenclamide. Accordingly, glibenclamide has a better effect on nocturnal and fasting blood glucose levels, but its use may also involve a greater risk of long-lasting hypoglycemia. At daily dosages of 5 mg or more, divided dosage seems unnecessary with glipizide, since effective concentrations will prevail throughout most of a 24 hour period. Efficacy may be improved if either drug is administered before, rather than together with, breakfast. High doses of glipizide may impair, rather than improve, glucose balance.