Acarbose

Acarbose is a pseudotetrasaccharide in which one maltose is exchanged for a pseudomaltose (Fig. 27). 

Although the data on HbAj reduction by about 1% (an indicator of possible late injuries) are contradictory, this may be the major reason to use acarbose. Serum cholesterol, triglycerides and the LDL/HDL ratio are 

The metabolism of skeletal-muscle glycogen is unaffected because of the inability of acarbose to be absorbed (see below) (Calder and Geddes, 1989). 

Rabbits fed 30 mg/day acarbose showed reduced levels of plasma cholesterol, intermediate-density lipoprotein (IDL) and LDL (Kritchevsky et al., 1990) sudanophilia was reduced by 23% in rabbits fed 7.5 mg/day acarbose and by 43% in rabbits fed 15 or 30 mg/day (Kritchevsky et al., 1990). The decrease in total cholesterol was shown to be a consequence of a significant reduction in LDL cholesterol. Since HDL cholesterol concentrations remained unal- 

Acarbose is used in diabetes in addition to other therapeutic regimes in connection with diet. Its clinical usefulness was demonstrated (Hanefeld et al., 1991) but its extent is a matter of controversy. However, a diet is preferable in Type-II diabetes. There are some studies which show the usefulness of its combination with sulphonylureas. Considerable individual variation is noted in the response to acarbose (Reaven et al., 1990). The use of acarbose in patients with NIDDM not well controlled by sulphonylureas appears to have significant clinical benefit (Raptis et al., 1982). One study suggests that it is not an effective substitute for sulphonylureas in non-obese Type-II diabetes uncontrolled by diet alone (Buchanan et al., 1988). 

Acarbose is a glucopyranose derivative that acts by inhibiting intestinal a-gluco-sidase. This delays carbohydrate absorption and reduces the postprandial (1.5 hours after food) blood glucose levels and is used in combination with other sulfonyl-ureas. Acarbose may cause GI disturbances, flatulence, abdominal distortion, diarrhea, and pain. Acarbose should be avoided during pregnancy, as it affects the fetus. Acarbose is contraindicated in inflammatory bowel disease and hepatic dysfunction. 

Molecular formula C25H43NO18 Molecular weight 645.60 CAS Registry No 56180-94-0 Merck Index 13,18 

Sample preparation Powder tablet, extract 3 times with 5 mL aliquots of wat with sonication for 15 min with vortexing at 5 min intervals each tim centrifuge at 2750 g for 5 min, combine supernatants, make up to 20 mL with water. Dilute a 50 p.L aliquot to 1 mL with MeOH, filter (0.2 aM), inject a 20 ixL aliquot. 

Column 250 x 4.6 5 (xm Nucleosil-NH2 Mobile phase MeOH dichloromethane 65 35 Flow rate 1 Injection volume 20 

Retention time 4.1 Limit of detection 5 Lg/mL Limit of quantitation 15 xg/mL 

Cherkaoui, S. Daali, Y. Christen, P. Veuthey, J.-L. Development and validation of liquid chromatography and capillary electrophoresis methods for acarbose determination in pharmaceutical tablets J.Pharm.Biomed.Anal., 1998,18, 729-735. 

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Acarbose is a nonabsorbable a-glucosidase inhibitor which blocks the digestion of starch, sucrose, and maltose. The digestion of complex carbohydrates is delayed and occurs throughout the small intestine rather than in the upper part of the jejunum. Absorption of glucose and other monosaccharides is not affected. Acarbose is adrninistered orally three times a day and chewed with the first mouthful of food. 

The first member of this class, acarbose, was introduced in the early 1990s. a-Glucosidase inhibitors slow the intestinal process of carbohydrate digestion by competitive inhibition of the activity of a-glucosidase enzymes located in the brush border of the enterocytes... 

Acarbose and Miglitol These agents are specific inhibitors of intestinal glucosidases and reduce the conversion of sucrose and starch to glucose. Their main effect is a delay, not a complete inhibition, of the absorption of carbohydrates. Postprandial blood sugar excursions are effectively reduced. Because a small portion of the carbohydrates enters the colon, their microbial degradation frequently causes flatulence or... 

Other combination options Metformin or a Sulfonylurea plus Acarbose/Miglitol, or Pioglitazone/ Rosiglitazone or Repaglinide (with metformin), or Insulin... 

The a-glucosidase inhibitors, acarbose (Precose) and miglitol (Glyset), lower blood sugar by delaying die digestion of carbohydrates and absorption of carbohydrates in the intestine. 

The a-glucosidase inhibitors are contraindicated in patients with a hypersensitivity to the drug, diabetic ketoacidosis, cirrhosis, inflammatory bowel disease, colonic ulceration, partial intestinal obstruction or predisposition to intestinal obstruction, or chronic intestinal diseases. Acarbose and miglitol are used cautiously in patients with renal impairment or pre-existing gastrointestinal (GI) problems such as irritable... 

Several mono-carba-oligosaccharidic alpha amylase inhibitors, such as acarbose and its homologs, amylostatins, trestatins, oligostatins, adipo-sins, and so on, have been isolated from cultures of micro-organisms, and considerable interest in the biochemistry and chemistry of this class of inhibitors has been stimulated. The characteristic core-structure for inhibitory action is composed of a trihydroxy(hydroxymethyl)cyclohexene moiety and a 4-amino-4,6-dideoxy-D-glucopyranose moiety, bonded by way of an imino linkage at the allylic position. A similar structural unit has been found in the antibiotic validamycins. 

Likewise, complete synthesis of acarbose was conveniently accomplished by use of the anhydro derivative 392b prepared from maltotriose. Condensation of 392b with optically active 359 afforded two products, one of which was, after deprotection, shown to be identical to an authentic sample of acarbose. 

Several possible models can be discussed for the molecular basis of slow inhibition, but experimental evidence in support of one or the other is still lacking for glycosidases. A reversible chemical reaction at the active site, for example, formation of the cyclic imine 3 or a diffusion-controlled association with a trace of 3 in equilibrium with the 5-araino-5-deoxypyranose 1 can be precluded, because slow inhibition is also observed with 1-deoxynojirimycin and its analogs and with acarbose (see Section II,2,d) and indoli-... 

APA from penicillin G, 7-ACA from cephalosporin C, 7-ADCA from desaacetoxy cephalosporin G Biotransformation in steroids, e.g. cortexolone to hydrocortisone and prednisolone Food additives Lactic Acid (now a bulk chemical for making polylactate). Citric acid, L-Glutamate, L-Lysine, etc. Vitamines C, B2, B12 Acarbose (antidiabetic drug)... 

Oral hypoglycemics Sulfonylureas Biguanides Th iaz o 1 idinediones Acarbose... 

Acarbose (Precose) and miglitol (Glyset) are dosed similarly. Therapy is initiated with a very low dose (25 mg with one meal a day) and increased very gradually (over several months) to a maximum of 50 mg three times daily for patients weighing 60 kg or more, or 100 mg three times daily for patients above 60 kg. The drugs should be taken with the first bite of the meal so that the drug is present to inhibit enzyme activity. 

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