The bioavailability of two beta-blockers preadsorbed onto charcoal

The relative bioavailability of metoprolol and pindolol from capsules containing the drug preadsorbed onto activated charcoal (100 mg metoprolol tartrate/120 mg charcoal and 10 mg pindolol/20 mg charcoal) was studied in two separate studies, in healthy volunteers, using randomized, crossover designs. The metoprolol control was a capsule containing the drug only and the pindolol control was a conventional tablet. In an in vitro dissolution study, both control formulations showed a rapid, total release of the drug, whereas from each of the drug-charcoal complexes, around 30% of the drug was released rapidly after which the release continued more slowly, reaching 45-60% in 24 h. The absorption of metoprolol and pindolol was slower from the charcoal formulations than from the control formulations. Charcoal, however, also essentially decreased the bioavailability, reducing the mean AUC0-24h and the mean 24 h urinary excretion of both metoprolol and pindolol to one-half and the mean plasma Cmax to one-third compared to the control. The increase in the mean tmax was not statistically significant. These results indicate that desorption of metoprolol and pindolol from charcoal occurs in the human gastrointestinal tract, but the bioavailability remains low. In spite of the sustained in vitro release of both drugs, the absorption was only slightly retarded at these charcoal:drug ratios.