The effect of a single or multiple doses of grapefruit juice on some pharmacokinetic and pharmacodynamic effects of paracetamol in mice

Grapefruit juice (GFJ), a commonly consumed dietary substance, has been shown to alter the disposition of several commonly used drugs. The available data on the effects of GFJ on the paracetamol pharmaco-kinetics and pharmacodynamics are at variance. The aim of this study was to evaluate the effect of single or multiple doses of GFJ on some pharmacokinetics and pharmacodynamics aspects of orally given paracetamol (400 mg/kg). Male mice were randomly divided into three equal groups: mice in the first group were given paracetamol; the second group was given a single oral dose (10 mL/kg) of GFJ one hour prior to paracetamol administration; the third group was administered multiple oral doses of GFJ (10 mL/kg) for five consecutive days, and on the last day it was treated with paracetamol. Blood samples were collected 10, 20, 30, and 40 min, and 1, 2, 4, 6 and 8 h after paracetamol administration for subsequent pharmacokinetic analysis. Some mice in the same three groups were also tested for their reactions to thermal (hotplate) and chemical (acetic acid-induced - abdominal constriction) nociceptive stimuli. GFJ increased the plasma concentration and area under the plasma concentration curve of paracetamol, to a greater extent after a single dose than multiple doses. It also increased the reaction time in the hotplate test and reduced abdominal constrictions. GFJ administration increased the plasma concentration and the analgesic effect of paracetamol in mice. The possible implications of these changes in humans and their clinical relevance need to be further investigated.