Acetohexamide agents

An example of this hydroxylation pathway is seen in the metabolism of the oral hypoglycemic agent acetohexamide... 

Dimelor acetohexamide. dimenhydrinate diphenhydramine, dimepheptanol [ban, inn] (methadol NIH 2933) is one of the phenylpiperidine series, an OPIOID RECEPTOR AGONIST, which is active as an OPIOID ANALGESIC. It is also elaborated in a number of close analogues, derivatives or diastereoisomers with similar properties. These include methadyl acetate [ban, usan] = acetylmethadol [inn] alphamethadol (ban, inn] alphacetylmethadol [inn] levomethadyl levacetylmethadoi [inn] = levomethadyl acetate (usan) betamethadol [ban, usan) betacetylmethadol (inn) = betacemethadone. dimepropion [ban] (metamfepramone [inn]) is an ephedrine-like agent with SYMPATHOMIMETIC and CNS STIMULANT properties. It can be used as an appetite SUPPRESSANT. 

C. Strickland14 described a method for the separation and detection of four of the more important oral hypoglycemic agents using thin-layer chromatography. It was used for the identification of acetohexamide, chlorpropamide, tolbutamide, and phenformin hydrochloride. 

TABLE 1 Comparison of Orally Administered Characteristics Tolbutamide Sulfonylurea Hypoglycemic Agents Acetohexamide Tolazamide Chlorpropamide Glipizide Glyburide... 

Acetohexamide is a blood-glucose-lowering drug of the sulfonylurea class. The first-generation oral hypoglycemic agents include tolbutamide (Orinase), acetohexamide (Dymelor), tolazamide (Tolinase), and chlorpropamide... 

The first-generation sulfonylureas vary considerably in their half-lives and extents of metabo-hsm. The tj of acetohexamide is short, but it is reduced to an active compound whose tj is similar to those of tolbutamide and tolazamide (4-7 hours). These drugs may require divided daily doses. Chlorpropamide has a long (24-48 hours). The second-generation agents are approximately... 

Reaction of acetohexamide with 2,4-dinitrophenyl-hydrazine to produce the colored hydrazone was used by Amer and Walash (19) to determine the drug colorimetri-cally. The colored product was dissolved in KOH and determined at 480 nm. The accuracy of the method was claimed to be 100. A ninhydrin colorimetric method for some oral hypoglycemic agents was also reported (20b). 

Meier et al (22) analysed acetohexamide and other hypoglycemic agents by dissolving the drug in chloroform, adding calcium acetate (IX in methanol), propylamine (5 in methanol), diluting with chloroform and reading the absorbance at 565 nm after 15 minutes. Pharmaceutical preparations may be estimated similarly. 

Acetohexamide and other sulphonylureas were analysed by IR (22). A test have also been described (24). Lazaryan (26) determined the drug and other hypoglycemic agents by infra-red absorptlometric determination. A sample is treated with chloroform and the solution from the tablet sample is filtered. A portion of solution is diluted with chloroform and the absorbance is measured at 1722 to 1715 cm in 0.25 mm NaCI cell against chloroform. 

Acetohexamide is used as an oral antidiabetic agent for the treatment of ketoacidosis-resistant diabetes. It is an intermediate acting sulfonylurea derivative. The clinical effects of lowering elevated blood glucose levels Is similar for all of the sulfonylurea derivatives. Acetohexamide, however. Is the only one to also possess uricosuric activity and therefore Is a preferable agent to treat diabetic patients with gout. 

Like other oral antidiabetic agents, acetohexamide may be used In combination with insulin to reduce Insulin requirements In Insulin dependent maturity onset diabetics and to reduce the potential for a hypoglycemic reaction. 

Nagamine et al (55) estimated the rates of available fraction for 4-acetam1doacetophenone, 4-acety1benzene-sulfonamide, and acetohexamide and their respective reduced compounds, 4-subst1tuted o-hydroxyethylphenyl derivatives. In rats. The study Indicated that the compounds are in a reversible drug-metabolite relationship. The pharmacokinetic profiles of the agents were studied after an Intraportal administration... 

In 1946, Loubatiere described the hypoglycemic effect of sulfonylureas. These compounds now are important in the treatment of diabetes. The two major categories of hypoglycemic agents are the sulfonylureas (tolbutamide, chlorpropamide, acetohexamide, and tolazamide), and the biguanides. 

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