To examine whether hyperglycaemia impairs the absorption of sulphonylurea agents, glipizide, which is rapidly and completely absorbed, was measured in plasma from 12 healthy young subjects during various levels of experimentally-induced hyperglycaemia. An increase in the plasma glucose concentration above 7 mmol/l was associated with a dose-dependent delay in the absorption of glipizide; at a concentration above 11 mmol/l, the plasma glipizide concentration was reduced by 50%. The data indicate that hyperglycaemia may delay the absorption of sulphonylurea agents, probably because it impairs gastric motility and/or gastric emptying. This delay of absorption may be clinically relevant, since the efficacy of short-acting sulphonylureas is dependent upon the absorption rate of the drug.
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