Effects of charcoal, sodium bicarbonate, and ammonium chloride on chlorpropamide kinetics

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Abstract
The effects of activated charcoal, sodium bicarbonate and ammonium chloride by mouth on chlorpropamide [an antidiabetic drug] kinetics was studied in 6 healthy subjects. Activated charcoal, 50 g, given immediately after 250 mg chlorpropamide reduced its absorption by 90%; but when given in repeated doses from 6 h on (50 g followed by 12.5 g at 6-h intervals), it did not shorten the chlorpropamide half-life (t1/2). The t1/2 of chlorpropamide was shortened from 49.7 .+-. 7.4 to 12.8 .+-. 1.1 h by sodium bicarbonate and prolonged to 68.5 .+-. 1.05 h by ammonium chloride. The 72-h urinary excretion of chlorpropamide was increased 4-fold by alkalinization and decreased to 1/20 of baseline by acidification of the urine. The renal clearance of chlorpropamide correlated with urinary pH, ranging from 1 to 1000 ml/h at pH 5-8. Urinary pH is likely to explain at least a part of great interindividual differences in the serum chlorpropamide concentrations during steady-state and variations in amount of urinary metabolites. In chlorpropamide intoxications, activated charcoal can reduce absorption and alkalinization of the urine accelerates its elimination.

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