Enhancement of morphine clearance following intravenous administration by oral activated charcoal in rabbits

A single dose of activated charcoal (10 g) significantly reduced the half-life of elimination (1.02 +/- 0.10 and 0.70 +/- 0.04 h for the control and treated groups, respectively) and mean residence time (1.01 +/- 0.12 and 0.76 +/- 0.05 h for the control and treated groups, respectively) of morphine in rabbits. A 40% increase in the systemic clearance (85.73 +/- 7.72 and 122.64 +/- 16.32 mL min-1 kg-1 for the control and treated groups, respectively) and a 30% decrease in AUC (204.38 +/- 22.20 and 140.03 +/- 19.32 micrograms h L-1 in the control and treated groups, respectively) were also noted. Charcoal administration did not significantly alter the volume of distribution (Varea and Vss) or the apparent distribution half-life. A two-compartment model adequately described morphine kinetics in control and treated rabbits; charcoal administration produced a significant increase in the tissue compartment rate constant (K21). This finding indicates that activated charcoal not only enhances the systemic elimination of morphine, but also accelerates the rate of transfer of morphine from the tissue compartment to the central compartment.