Effect of fresh pomegranate juice on the pharmacokinetic profile of artemether: An open-label, randomized, 2- period crossover study in healthy human volunteers

Abstract

This study was designed to evaluate the effect of fresh pomegranate (Punica granatum L.) juice on the pharmacokinetic profile of artemether in healthy volunteers. A randomized, open-label, crossover study was conducted on healthy subjects (n = 26). Each volunteer received 250 mL of fresh pomegranate juice twice daily for 2 weeks. On day 14, they were administered a single oral dose of artemether (80 mg) with either water or 250 mL of pomegranate juice. Thirteen blood samples were collected up to 12 h and 6 electrocardiograms were recorded. Plasma concentrations of artemether and its metabolite dihydroartemisinin were analyzed by a noncompartmental method using LC–MS/MS. The lower limit of detection (LLOD) and lower limit of quantification (LLOQ) for artemether were estimated as 0.3 and 0.8 ng/mL, respectively, while for dihydroartemisinin it was 0.2 and 0.6 ng/mL, respectively. The pharmacokinetic parameters of artemether and dihydroartemisinin were not significantly altered when co-administered with the fresh pomegranate juice. AUC (0-∞) was slightly increased from 742 to 859 ng/mL for artemether [geometric mean ratio: 1.14 (95 % CI, 1.08,1.18); P = 0.45] and from 699 to 818 ng/mL for dihydroartemisinin [geometric mean ratio: 1.15 (95 % CI, 1.09, 1.15); P = 0.4]. Difference in Cmax for artemether was also statistically non-significant [173 vs 195 ng/mL; geometric mean ratio: 1.09 (95 % CI, 0.91, 1.15); P = 0.61]. Likewise, elimination half-life (t1/2) for both artemether and dihydroartemisinin remained unchanged (P = 0.43 and 0.31, respectively). In addition, there was no significant difference in tmax for artemether (P = 0.66) and its metabolite (P = 0.65). In conclusion, findings of the present study demonstrated that the administration of pomegranate juice had no significant effect on the pharmacokinetic profile of artemether.