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 gra pefruit juice on metabolism on many drags. It has been reported that grapef ruit juice increases the plasma concentrations of orally administrated drug s, that undergo metabolism in liver. However, all these experiments were do ne with a single dose of grapefruit juice. The primary aim of this study wa s to evaluate if the chronical ingestion of grapefruit juice could also cau se these effects. Paracetamol is metabolized by reactions of oxidation and conjugation to nontoxic ineffective metabolites. These reactions, partly ca talyzed by cytochrome P450 izoenzymes, take place in liver. The analgesic e ffect of paracetamol was examined by Writhing tests, where we used acetic a cid as an irritating agent. We used three groups of male mice: the control group, the group which was administrated 0.2 mt of grapefruit juice per os 10 days (GPOch) and the group which was administrated single dose of 0.5 mt 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 % ace- tic 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 effe ct in GPOch group than in the control group and less irritant effect in GPO ac group than in the control group. In the period of 5-15 min, after the ap plication, paracetamol shows analgesic effect neither in the control nor in the other groups.