Pharmacokinetic interactions between indomethacin and paracetamol in the rat

The influence of concurrent administration of paracetamol with indomethacin on the plasma concentrations of these drugs was studied in rats. Orally administered paracetamol reduced the plasma levels of indomethacin during the first 2 hours after oral administration. Later, 16 and 24 hours after administration of indomethacin, the plasma levels exceeded the control values due to the concurrent oral administration of paracetamol. These data suggest that paracetamol delayed the absorption of indomethacin. In contrast the plasma concentrations of paracetamol were not influenced substantially by indomethacin. When paracetamol was co-administered subcutaneously with oral indomethacin, the plasma levels of the latter drug were not influenced. It is concluded that the protective effect of paracetamol against the gastric injuring side effect of indomethacin, which also occurs with subcutaneous administration of paracetamol, cannot be solely due to lowered plasma concentrations of indomethacin.