Interaction of White and Pink Grapefruit Juice with Acetaminophen (Paracetamol)In Vivoin Mice

Abstract

Grapefruit juice increases bioavailability of a number of drugs because of inhibition of the P-glycoprotein pump and inhibition of intestinal cytochrome P450 3A4 enzyme. However, interaction between acetaminophen (also known as paracetamol in many parts of the world) and grapefruit juice has never been reported. The interaction of grapefruit juice with acetaminophen was examined in an in vivo mouse model. BALB/c mice were fed 200 microL of white grapefruit juice or pink grapefruit juice by oral gavage (three mice in each group) followed by oral delivery of 10, 50, or 100 mg/kg acetaminophen 1 hour later. Blood was withdrawn from the retro-orbital venous plexus at 1 hour and 2 hours after feeding with acetaminophen. The concentrations of acetaminophen in sera of mice were determined by fluorescence polarization immunoassay. White grapefruit juice increased concentrations of acetaminophen in mice both 1 hour and 2 hours after feeding compared to controls. In contrast, pink grapefruit juice increased acetaminophen concentrations 2 hours after feeding compared to controls. Because acetaminophen is almost completely absorbed these effects seems to be related to increased elimination half-life of acetaminophen because of interaction with grapefruit juice.

The Effect of a Single or Multiple Doses of Grapefruit Juice on Some Pharmacokinetic and Pharmacodynamic Effects of Paracetamol in Mice

“…These findings are in line with the observed increase in paracetamol plasma concentrations. However, contrary to our present results and those of Dasgupta et al, Qinna et al found that frequent administration of GFJ reduced the oral bioavailability of paracetamol in rats (19)(20)(21). This discrepancy might be related to species differences.…”

“…GFJ-paracetamol interaction has not drawn a lot of attention because of the small portion of paracetamol that undergoes cytochrome P450 enzymes metabolism. Dasgupta et al and Samojlik et al have shown that GFJ increased the concentrations of paracetamol in mice compared with the control after single and multiple doses, respectively (19)(20). On the contrary, Qinna et al reported a reduced bioavailability of paracetamol following multiple GFJ administration in rats and reduced salivary levels of paracetamol in human saliva following a single dose of GFJ (21)(22).…”

Pharmacoinformatic Approaches to Design Natural Product Type Ligands of ABC-Transporters

“…These include mainly flavonoids found in fruit juices, vegetables, flowers and tea. Especially grapefruit juice has been shown to interfere with plasma levels of colchicines [54], paracetamol [55], and cyclosporine [56].…”

Interaction Between Grapefruit Juice and Drugs

“…For example, acetaminophen/paracetamol (Tylenol) concentrations were found to be increased in murine blood by white and pink grapefruit juice, with the white juice acting faster [13]. Interestingly, "the bioavailability of paracetamol was significantly reduced following multiple GFJ administration" in mice and rats.…”

“…Interestingly, "the bioavailability of paracetamol was significantly reduced following multiple GFJ administration" in mice and rats. This suggests that repeated intake of grapefruit juice reduces the efficacy and bioavailability of acetaminophen/paracetamol in comparison to a single dose of grapefruit juice, which conversely increases the efficacy and bioavailability of acetaminophen/paracetamol [12,13]. Tassaneeyakul et al reported the effect of grapefruit juice intake on the disposition of omeprazole and its primary metabolites, following a single oral dose, to 13 healthy volunteers, two of whom being poor metabolisers for cytochrome P450 (CYP) 2C19 [14].…”