Background and Goal of Study: Grapefruit juice (GFJ) interacts with many drugs by inhibiting CYP3A enzyme or transporter proteins. Oxycodone is an opioid, which is predominantly metabolized by CYP3A (1). This study was aimed to investigate the effect of repeated intake of GFJ on the pharmacokinetics and pharmacodynamics of oral oxycodone.
Materials and Methods: A randomized, crossover study design was used. 12 healthy volunteers ingested 200 ml GFJ or water t.i.d. for 5 days. Oral oxycodone hydrochloride 10 mg was administered on day 4. Oxycodone, noroxycodone, oxymorphone and noroxymorphone concentrations were measured for 48 hours and pharmacokinetic parameters were calculated by standard methods. Behavioural and analgesic effects were recorded for 12 hours. Student's t-test and Wilcoxon signed rank test were used for statistical analysis.
Results and Discussion: Oxycodone (mean±SEM) plasma concentrations are shown in Figure 1. After GFJ, the peak concentration of oxycodone increased from 18.9±4.7 to 26.8±4.0 ng/ml (P<0.001) and the area under plasma concentration-time curve from 7.3±2.1 to 11.8±2.7 ìg·min/ml (P<0.001). The formation of noroxymorphone decreased from 1.02±0.38 to 0.56±0.22 (P<0.001) as assessed by the metabolite-to-parent drug area under plasma concentrationtime curve ratio. During GFJ, the deteriorating effect of oxycodone on self-rated performance increased significantly (P<0.05). The observed changes are in agreement with the known effects of GFJ on CYP3A activity.
Conclusion(s): GFJ significantly inhibited the metabolism of oxycodone and increased its concentrations. These changes were accompanied by small increase in the pharmacologic response to oxycodone. GFJ may increase the plasma concentrations and clinical effects of oxycodone.
1 Lalovic B, Phillips B, Risler LL et al. Quantitative contribution of CYP2D6 and CYP3A to oxycodone metabolism in human liver and intestinal microsomes. Drug Metab Dispos. 2004;32:447-54.