Grapefruit juice has no effect on quinine pharmacokinetics

Objective: As quinine is mainly metabolised by human liver CYP3A4 and grape fruit juice inhibits CYP3A4, the effect of grapefruit juice on the pharmaco kinetics of quinine following a single oral dose of 600 mg quinine sulphate was investigated. Methods: The study was carried out in ten healthy volunteers using a random ised cross-over design. Subjects were studied on three occasions, with a wa shout period of 2 weeks. During each period, subjects received a pretreatme nt of 200 mi orange juice (control), full-strength grapefruit juice or half -strength grapefruit juice twice daily for 5 days. On day 6, the subjects w ere given a single oral dose of 600 mg quinine sulphate with 200 mi of one of the juices. Plasma and urine samples for measurement of quinine and its major metabolite, 3-hydroxyquinine, were collected over a 48-h period and a nalysed by means of a high-performance liquid chromatography method. Results: The intake of grapefruit juice did not significantly alter the ora l pharmacokinetics of quinine. There were no significant differences among the three treatment periods with regard to pharmacokinetic parameters of qu inine, including the peak plasma drug concentration (C-max), the time to re ach C-max (t(max)), the terminal elimination half-life (t(1/2)), the area u nder the concentration-time curve and the apparent oral clearance. The phar macokinetics of the 3-hydroxyquinine metabolite were slightly changed when volunteers received grapefruit juice. The mean C-max of the metabolite (0.2 5 +/- 0.09 mg l(-1), mean +/- SD) while subjects received full-strength gra pefruit juice was significantly less than during the control period (0.31 /- 0.06 mg l(-1), P < 0.05) and during the intake of half-strength grapefru it juice (0.31 +/- 0.07 mg l-(1), P < 0.05). Conclusion: These results suggest that there is no significant interaction between the parent compound quinine and grapefruit juice, so it is not nece ssary to advise patients against ingesting grapefruit juice at the same tim e that they take quinine. Since quinine is a low clearance drug with a rela tively high oral bioavailability, and is primarily metabolised by human liv er CYP3A4, the lack of effect of grapefruit juice on quinine pharmacokineti cs supports the view that the site of CYP inhibition by grapefruit juice is mainly in the gut.