Major Furocoumarins in Grapefruit are Detectable in Plasma Following Consumption of Grapefruit and Grapefruit Juice

Furocoumarins are aclass of organic compound found in a variety of vegetables and fruits, especially citrus fruits. Grapefruit is a relatively common source of furocoumarins, and because of this, the term “grapefruit effect” has become a popular way of referring to the interactions between furocoumarins and enzymes involved in drug metabolism, especially cytochrome P450. Ingested furocoumarins are also known to cause phytophotodermatitis. For these reasons, determining the absorption of furocoumarins from diet is of great interest. The objective of this study was to determine the presence and concentrations of 7 furocoumarins in grapefruit and grape fruitjuice and to quantify their bioavailability in the blood following ingestion. A total of 9participants (6 males and 3 females) were recruited and randomly assigned to consume either the flesh of 2 whole grapefruits (approximately 494 g; n=4) or470 ml of grapefruit juice (approximately 485 g; n=5). Plasma was collected from each participant at 11 time points (fasted and 0.25, 0.5, 1, 2, 3, 4, 5,6, 7, and 8 hours following ingestion). The concentrations of 7 furocoumarins(bergaptol, psoralen, 8‐methoxypsoralen (8‐MOP), bergapten,6′,7′‐dihydroxybergamottin (6′,7′‐DHB), epoxybergamottin, and bergamottin) were measured in plasma samples using UPLC‐MS/ MS. The concentrations of furocoumarins in grapefruit juice and flesh were determined, and plasma concentrations were measured at each time point for individual participants. From these values the average maximum concentration (C max ), area under the curve (AUC), and the times of minimum (T min ) and maximum (T max )detectable concentration (median, (min, max)) were calculated to assess bioavailability of furocoumarins in plasma. The furocoumarins detected in grapefruit juice (mean + SD, ng/g) were bergamottin (9,374.8±397.4), 6′,7′‐DHB (1,648.8 ± 58.0), bergaptol (1,477.6 ±38.3), and bergapten (30.3 ± 3.2). The furocoumarins detected in grape fruitflesh were bergamottin (11,927.1 ± 161.4), 6′,7′‐DHB (2,806.5 ±73.8), epoxybergamottin (448.4 ± 1.7), and bergaptol (286.5 ± 7.1). Only bergamottin and 6′,7′‐DHB were detected in plasma. Bergamottin was not detected in the plasma of 2 participants, both of whom had consumed whole grapefruit. The C max , T max , and T min of bergamottin were 1.44 ±0.20 ng/g, 1 hour (0.5, 2), and 3 hours (1, 5), respectively. The C max , T max , and T min of 6′,7′‐DHB were 2.32 ±0.27 ng/g, 0.5 hours (0.5, 5) and 1 hour (0.5, 5). The mean AUC (ng × min/g) in plasma was 217.2 ± 104.1 for bergamottin and 269.4±148.9for 6′,7′‐DHB. In general, plasma concentrations of bergamottin and 6′7′‐DHB reached higher levels in participants consuming grapefruit juice than those consuming whole fruit ( Figures 1 and 2). Grapefruit juice and whole grapefruit are rich sources of furocoumarins, especially bergamottin,6′,7′‐DHB, and bergaptol. Both bergamottin and 6′,7′‐DHB were detectable in plasma as early as 15 minutes after ingestion and were still observed in most participants up to 3 or more hours after ingestion. Support or Funding Information University of Connecticut REP grant awarded to Dr. Ock Chun