Pharmacokinetic-pharmacodynamic relationships of Acarbose

Clin Pharmacokinet. 1996 Feb;30(2):94-106. doi: 10.2165/00003088-199630020-00002.

Abstract

Acarbose represents a new pharmacological approach to achieving the metabolic benefits of a slower carbohydrate absorption in diabetes, by acting as a potent, competitive inhibitor of intestinal alpha-glucosidases. Acarbose molecules attach to the carbohydrate binding sites of alpha-glucosidases, with an affinity constant that is much higher than that of the normal substrate. Because of the reversible nature of the inhibitor-enzyme interaction, the conversion of oligosaccharides to monosaccharides is only delayed rather than completely blocked. Acarbose has the structural features of a tetrasaccharide and does not cross the enterocytes after ingestion. Thus, its pharmacokinetic properties are well suited to the pharmacological action directed exclusively towards the intestinal glucosidases. The most important clinical consequence of the delayed carbohydrate digestion caused by acarbose is the attenuation of postprandial increases in blood glucose levels. Other effects have also been described: a decreased beta-pancreatic response to meals, and influences on gut hormone secretion and plasma lipid levels. Gastrointestinal discomfort is frequently reported as an adverse effect of acarbose administration, but incidence usually decreases with time. The suitability of acarbose for improving glucose homeostasis as an adjunct to dietary control or to administration of sulphonylureas or insulin has been extensively studied in patients both with type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus. Acarbose can be used as first-line therapy in patients with type 2 diabetes which is poorly controlled by diet alone. Moreover, the lack of bodyweight gain or hypoglycaemic effects reported during acarbose treatment may be advantageous for obese or elderly patients. Finally, the reduction in fluctuations of glucose levels throughout the day may help to control type 1 diabetes in patients with 'brittle diabetes'. Long term prospective studies are still needed to confirm these indications and the usefulness of acarbose in conditions other than diabetes, notably reactive hypoglycaemia and dumping syndrome.

Publication types

  • Review

MeSH terms

  • Acarbose
  • Administration, Oral
  • Arteriosclerosis / drug therapy
  • Blood Glucose / metabolism
  • Diabetes Mellitus / drug therapy
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / pharmacokinetics*
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Hypoglycemia / drug therapy
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / pharmacokinetics*
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Injections, Intravenous
  • Islets of Langerhans / drug effects
  • Risk Factors
  • Trisaccharides / administration & dosage
  • Trisaccharides / adverse effects
  • Trisaccharides / pharmacokinetics*
  • Trisaccharides / pharmacology
  • Trisaccharides / therapeutic use

Substances

  • Blood Glucose
  • Enzyme Inhibitors
  • Hypoglycemic Agents
  • Trisaccharides
  • Acarbose