Allopurinol |
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Click here for the general idea of Allopurinol
Proprietary Names: Lopurin, Zyloprim. Chemical Name: 1H-pyrazolo[3,4-d]pyrimidin-4-ol. Synthesis: Condensation of hydrazine with ethoxymethylenemalononitrile (I) leads to 3-amino-4-cyanopyrazole (II), which, by hydrolysis with sulphuric acid, gives the corresponding amide (III); heating III with formamide in excess results in allopurinol (IV). The synthesis of allopurinol can be illustrated as below:
Properties: Fluffy white to off-white, odourless or almost odourless, tasteless, microcrystalline powder. It is very slightly soluble in water and alcohol, soluble in dimenthylformamide and in dilute solutions of potassium and sodium hydroxides, and practically insoluble in chloroform and ether. Uses: Because it decreases the biosynthesis of uric acid, it is used to reduce hyperuricemia in gout. It is the preferred drug in the treatment of tophaceous gout. It is also used in the management of recurrent calcium oxalate kidney stones. Biotrasformation: It is metabolised by xanthine oxidase to oxypurinol, also an inhibitor of this enzyme. Allopurinol and oxypurinol are not bound to serum proteins; they are eliminated mainly in urine. Incompatibilities: It increases the serum half-life of sulfonylureas and inhibits the enzymatic oxidation of mercaptopurine. Its clinical effectiveness is decreased when taken concurrently with probenecid. Bioavailability: Given by oral route, about 80% of the dose is absorbed and peak serun concentrations are attained in 1 to 2 hours; oxypurinol, the major metabolite, reaches peak concerntrations in 6 hours. The half-life of allopurinol is 1.3 hours and that oxypurinol is about 21 hours. Dosage: By oral route, dosage must be individualized; initially, 100 mg daily, increased at weekly intervals by 100 mg. Storage: In airtight containers. Assay: Spectrophotometric1.
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