The effect of paracetamol on peritoneal reflex after single and multiple grapefruit ingestion

In the last few years, more attention has been paid to the influence of grapefruit juice on metabolism on many drugs. It has been reported that grapefruit juice increases the plasma concentrations of orally administrated drugs, that undergo metabolism in liver. However, all these experiments were done with a single dose of grapefruit juice. The primary aim of this study was to evaluate if the chronical ingestion of grapefruit juice could also cause these effects. Paracetamol is metabolized by reactions of oxidation and conjugation to nontoxic ineffective metabolites. These reactions, partly catalyzed by cytochrome P450 izoenzymes, take place in liver. The analgesic effect of paracetamol was examined by Writhing tests, where we used acetic acid as an irritating agent. We used three groups of male mice: the control group, the group which was administrated 0.2 mL of grapefruit juice per os 10 days (GPOch) and the group which was administrated single dose of 0.5 mL grapefruit juice per os 90 min. before the experiment (GPOac). Dose of 50 mg/kg of paracetamol was applicated s.c. 5 min. before i.p. application of 3 % acetic acid. The writhing phenomenon was observed in periods of 5-15 min. and 15-30 min. after the application of paracetamol. The results show that paracetamol in GPOch group significantly decreases irritant effect of acetic acid in the period of 15-30 min. after the application in relation to the control group. However, the acetic acid shows stronger irritant effect in GPOch group than in the control group and less irritant effect in GPOac group than in the control group. In the period of 5-15 min. after the application, paracetamol shows analgesic effect neither in the control nor in the other groups.