Sodium bicarbonate Chlorpropamide

Oral administration of bicarbonate may decrease the absorption of ketoconazole. Increased blood levels of quinidine, flecainide, or sympatiiomimetics may occur when these agents are administered with bicarbonate There is an increased risk of crystalluria when bicarbonate is administered with the fluoroquinolones. Fbssible decreased effects of lithium, methotrexate, chlorpropamide, salicylates, and tetracyclines may occur when these drag s are administered with sodium bicarbonate. Sodium bicarbonate is not administered within 2 hours of enteric-coated drugs the protective enteric coating may disintegrate before the drug reaches the intestine. 

Urine alkalinization is a treatment modality that increases elimination of poisons by the intravenous administration of sodium bicarbonate to produce urine with a pH of more than or equal to 7.5 and must be supported by high urine flow. This technique might be useful for the elimination of drugs with an acid pKa such as salicylates (but not recommended for phenobarbital intoxication for which multiple-dose activated charcoal is better), chlorpropamide, 2,4-dichlorophenoyacetic acid, diflunisal, fluoride, mecoprop, methotrexate. Complications include severe alkalemia, hypokalemia, hypocalcemia and coronary vasoconstriction. 

A study in 6 healthy subjects given a 250-mg oral dose of chlorpropamide found that when the urine was made alkaline (pH 7.1 to 8.2) with sodium bicarbonate, the half-life of the chlorpropamide was reduced from 50 to 13 hours, and the 72-hour clearance was increased fourfold. In contrast, when the urine was acidified (pH 5.5 to 4.7) with ammonium chloride, the chlorpropamide half-life was increased from 50 to 69 hours and the 72-hour urinary clearance was decreased to 5%, and non-renal (i.e. metabolic) clearance predominated. Another study found that the renal clearance of chlorpropamide was almost 100 times greater at pH 7 than at pH 5. The reasons are that changes in urinary pH affect the ionisation of the chlorpropamide, and this affects the ability of the kidney to reabsorb it from the kidney filtrate (see more details under Drug excretion interac-... 

There appear to be no reports of adverse interactions between chlorpropamide and drugs that can alter urinary pH, but prescribers should be aware of the possibilities a reduced response if the pH is raised significantly and renal clearance predominates (e.g. with sodium bicarbonate, acetazolamide, some antacids) an increased response if the pH is made more acid than usual and metabolic clearance predominates (e.g. with ammonium chloride). Perhaps more importantly, the effects of drugs that alter the hepatic clearance of chlorpropamide are likely to be more significant when its renal clearance is low (i.e. when the urine is acid). ... 

Neuvonen PJ, Karkkainen S. Effects of charcoal, sodium bicarbonate, and ammonium chloride on chlorpropamide kinetics, Clin Pharmacol Ther( 9% S) 33, 386-93. 

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