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

The effects of activated charcoal, sodium bicarbonate, and ammonium chloride by mouth on chlorpropamide kinetics was studied in six healthy subjects. Activated charcoal, 50 gm, given immediately after 250 mg chlorpropamide reduced its absorption by 90%, but when given in repeated doses from 6 hr on (50 gm followed by 12.5 gm at 6-hr intervals) it did not shorten the chlorpropamide half-life (t 1/2). The t 1/2 of chlorpropamide was shortened from 49.7 +/- 7.4 to 12.8 +/- 1.1 hr by sodium bicarbonate and prolonged to 68.5 +/- 10.5 hr by ammonium chloride. The 72-hr urinary excretion of chlorpropamide was increased fourfold 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/hr at the pH from 5 to 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.