Accelerated clearance of intravenous indomethacin by oral activated charcoal in rabbits

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.