Abstract
The effect of oral activated charcoal on the systemic clearance and other pharmacokinetic parameters of intravenously administered indomethacin (2 mg /kg) was studied in rabbits. Following a single oral dose of activated charcoal (10 g), a significant reduction in indomethacin serum concentrations was observed. Charcoal treatment resulted m a significant decrease in the terminal elimination half-life (1.26 ± 0.14 and 0.82 ± 0.03 h for the control and treated groups, respectively) and the mean residence time (1.29 ± 0.14 and 0.79 ± 0.03 h for the control and treated groups, respectively). Further, a 68% increase in the systemic clearance (1.92 ± 0.19 and 3.23 ± 0.15 ml/min per kg for the control and treated rabbits, respectively) and 41% decrease in the area under the serum concentration-time curve (17.56 ± 1.82 and 10.34 ± 0.48
μg h/ml in the control and treated groups, respectively) were also noted. Charcoal administration did not significantly alter the volume of distribution (
V
c
,
V
ss
and
V
area
). Regarding the microconstants of the two-compartment phannacokinetic model which adequately described indomethacin kinetic in the control and treated rabbits, charcoal administration produced a significant increase in the rate of transfer of indomethacin from the tissue compartment to the central compartment (
K
21) and out of the central compartment (
K
10). The results indicate that administration of oral activated charcoal accelerates the systemic elimination of indomethacin. This is presumably mediated by interruption of the enterohepatic circulation of indomethacin by activated charcoal.