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Desorption of furosemide from charcoal in vitro and in man.

The gastrointestinal absorption of furosemide preadsorbed onto activated charcoal was studied in 8 healthy volunteers using a randomized cross-over design with 3 phases. The 3 experimental furosemide formulations were capsules containing 40 mg furosemide only (reference) or 100 mg furosemide preadsorbed onto 160 mg or 200 mg charcoal. Timed plasma samples were taken and urine was collected for 24 hours for determination of drug concentrations and diuretic response. The release of furosemide from the formulations was also studied in vitro. Furosemide was found to dissolve rapidly from the reference formulation, whereas it was slowly desorbed from charcoal with the cumulative release reaching 50-60% in 24 hours (pH 5.3). The absorption rate of furosemide was smaller after intake of the charcoal formulations that after intake of the reference formulation. However, also the amounts of furosemide found in plasma and urine were clearly decreased due to preadsorption onto charcoal. The dose-adjusted relative bioavailabilities of the furosemide-charcoal formulations (compared to the reference formulation) remained less than 10%. The release mechanism of furosemide from charcoal is sensitive to physiological factors of the gastrointestinal tract. The large variability known to be typical for furosemide absorption was further increased when the drug was preadsorbed onto charcoal.