Effect of oral charcoal and urine pH on dextropropoxyphene pharmacokinetics

The effects of orally given activated charcoal, sodium bicarbonate and ammonium chloride on the pharmacokinetics of dextropropoxyphene were studied in six volunteers in a randomized, cross-over study. Serum and urine concentrations of dextropropoxyphene and norpropoxyphene were determined by GLC up to 72 h. Activated charcoal (50 g) given 5 min after dextropropoxyphene hydrochloride (130 mg), reduced its absorption by 97-99%. When given in repeated doses from 6 h on, 50 g followed by 12.5 g at 6 h intervals, charcoal significantly shortened the terminal serum half-life of dextropropoxyphene from 31.1 +/- 4.2 h to 21.2 +/- 3.1 h (p less than 0.05) and that of norpropoxyphene from 34.4 +/- 2.5 h to 19.8 +/- 3.4 h (p less than 0.001), and reduced their excretion into urine. The cumulative urinary excretion of unchanged dextropropoxyphene was increased 6-fold by acidification and reduced to 1/20 by alkalinization of urine, but the excretion of norpropoxyphene was much less dependent on urinary pH. However, the cumulative excretion of dextropropoxyphene and norpropoxyphene even into acidic urine accounted for less than 25% of the dose during 72 h. Because urinary pH has a great influence on the ratio of urinary versus serum dextropropoxyphene concentrations, pH should be taken into consideration, when the clinical significance of its concentration in urine is evaluated. Activated charcoal in high doses effectively prevents the absorption of that fraction of dextropropoxyphene which is in the stomach at the time of charcoal administration. Given in repeated oral doses, charcoal increases to some extent the rate of elimination of dextropropoxyphene and norpropoxyphene, probably by interrupting their enterohepatic or enteroenteric circulation.