Chlorpropamide metabolites

Tolazamide is slowly absorbed and its hypoglycemic action only becomes manifest after several hours. Its is metabolized in the liver with an elimination half-life of about 7 hours. However several of its metabolites retain hypoglycemic activity. Its duration of action is shorter than that of chlorpropamide. 

Facial flushing after ingestion of alcohol occurs in up to one-third of patients taking chlorpropamide. The mechanism, like that of the disulfiram reaction, probably involves inhibition of the oxidation of acetaldehyde, a metabolite of ethanol. The plasma concentration of chlorpropamide may be correlated with chlorpropamide—alcohol flushing. 

Chlorpropamide 60 Metabolized by liver (-70%) to less active metabolites and excreted intact (-30%) by kidneys can potentiate antidiuretic hormone action taken once a day... 

High Pressure Liquid Chromatography. In serum chlorpropamide or tolbutamide, sensitivity 7 pg/ml for chlorpropamide, UV detection—R. E. Hill and J. Crechiolo,/. Chromat.y 1978,145 Biomed. AppL, 2,165-168. In urine chlorpropamide and metabolites, using initial separation by thin-layer chromatography, UV detection—J. A. Taylor, Clin. Pharmac. Ther., 1972, 75,710-718. 

Elimination. Renal blood flow, glomerular filtration and tubular secretion decrease with age above 55 years, a decline that is not signalled by raised serum creatinine concentration because production of this metabolite is diminished by the age-associated diminution of muscle mass. Indeed, in the elderly, serum creatinine may be within the concentration range for normal young adults even when the creatinine clearance is 50 ml/min (compared to 127 ml/min in adult male). Particular risk of adverse effects arises with drugs that are eliminated mainly by the kidney and that have a small therapeutic ratio, e.g. aminoglycosides, chlorpropamide, digoxin, lithium. 

Metabolism/ elimination Acetohexamide, chlorpropamide, tolazamide, glyburide glimepiride weakly active metabolites. Glipizide, tolbutamide inactive metabolites. Inactive metabolites Predominantly inactive metabolites Excreted unchanged in urine Extensively metabolized in liver to metabolites Acarbose inactive metabolites. Miglitol excreted unchanged in urine. 

Numerous barbiturates and oral hypoglycemic sulfonyl-ureas also have aliphatic side chains that arc su.sceptible to oxidation. Note that the sedative hypnotic amobarbital (Amytal) undergoes extensive to - I oxidation to the corresponding 3 -hydroxylated metabolite.Other barbiturates, such as pentobarbital, thiamylal,and secobarbital," reportedly are metabolized by way of a and to - I oxidation. The ri-propyl side chain attached to the oral hypoglycemic agent chlorpropamide (Diabinc.se) undergoes extensive to -I hydroxylation to yield the secondary alcohol 2 -hydroxy-chlorpropamide as a major urinary metabolite in humans. " ... 

Tolazamide, U5P. Tolazamide. l-(hexahydrn-l/f-azcpin-l-yl)-3-(/r-tolylsulfonyl)urea (Tolinase). is an analogue of tolbutamide and is reported to be effective, in general, under the same eireumstanccs in which tolbutamide is useful. Tolazamide, however, appears to be more potent than tolbutamide and is nearly equal in potency to chlorpropamide. In studies with radioactive tolazamide, investigators found that 85% of an oral dose appeared in the urine as metabolites that were more soluble than tolazamide itself. 

Acetohexamideis metabolized by reduction in the liver of its ketone function to an alcohol, hydroxyhexamide, which is pharmacologically active (79,86). After oral administration, the plasma concentration of the parent compound peaks in 1-2 h, then falls rapidly. The active metabolite has a longer half-life and prolongs the duration of action. Hydroxyhexamide is excreted primarily in the urine with a small amount of the parent and other clinically unimportant metabolites. Chlorpropamide is quite long lived in circulation, with an elimination half-life of about 36 h. It is slowly metabolized by hydroxylation at the 2 or 3 position of the propyl substituent, yielding metabolites that retain some activity and by N-dealkylation to p-chlorobenzenesulfonyl-urea (86, 89). Urinary excretion is the main... 

Miscellaneous drugs Hypoglycaemic agents Sulphonylurea, antidiabetic drugs like chlorpropamide or tolbutamide, in the presence of the respective metabolites of either extracted in ether from acidified plasma. Partition (i Bondapak Clg 0.05M ammonium formate/acetonitrile (83 17)... 

All the sulfonylureas are metabolized by the liver, and the metabolites are excreted in the urine. The metabolism of chlorpropamide is incomplete, and abont 20% of the drug is excreted unchanged. Therefore, snlfonylnreas should be administered with cantion to patients with either renal or hepatic insnfficiency. 

Also analyzed metabolites, acebutolol, acepromazine, acetaminophen, acetazolamide, ace-tophenazine, albuterol, alprazolam, amitriptyline, amobarbital, amoxapine, antipyrine, atenolol, atropine, azatadine, baclofen, benzocaine, bromocriptine, brompheniramine, bro-tizolam, bupivacaine, buspirone, butabarbital, butalbital, caffeine, carbamazepine, cetir-izine, chlorcyclizine, chlordiazepoxide, chlormezanone, chloroquine, chlorpheniramine, chlorpromazine, chlorpropamide, chlorprothixene, chlorthalidone, chlorzoxazone, cimeti-dine, cisapride, clomipramine, clonazepam, clonidine, clozapine, cocaine, codeine, colchicine, Qrclizine, cyclobenzaprine, demtrolene, desipramine, diazepam, diclofenac, diflunisal. 

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