Effect of Licorice and Grapefruit Juice on Paracetamol Pharmacokinetics in Human Saliva

The effect of grapefruit juice and liqorice juice on salivary pharmacokinetics of paracetamol (acetaminophen, APAP) in 8 healthy subjects (4 males and 4 females) was investigated. Paracetamol tablet (500 mg) was administered to the volunteers with either 240 mL grapefruit juice, licorice juice or water followed by saliva samples collection at different time intervals in a sequential study design with washout period of 3 days. Results have shown unexpected significant decrease in salivary Cmax and AUC of paracetamol due to grapefruit consumption with delay in Tmax (p < 0.05), while licorice consumption did not produce any significant changes in all tested parameters. However, a notable increase in the Cmax and AUC in females receiving licorice juice, but not in males, was revealed when compared to female control group. Therefore, in order to remove the confounding results of gender effect, the pharmacokinetic parameters of paracetamol following ingestion of grapefruit and licorice juice were analyzed for each sex separately and showed no differences within each gender when compared to the water control group. In addition, smoking had shown essentially no effect on paracetamol pharmacokinetics except a shift in Tmax when licorice juice was consumed. In conclusion, consuming grapefruit juice and licorice juice along with paracetamol could cause differences in the salivary pharmacokinetics of paracetamol and should be avoided until further clinical studies establish the safety of such interactions in both males and females.