Effect of grapefruit juice, naringin, naringenin, and bergamottin on the intestinal carrier-mediated transport of talinolol in rats.
The effect of two varieties of grapefruit juice (white and ruby red) and its selected components (naringin, naringenin, and bergamottin) was investigated on the activity of the P-glycoprotein (P-gp) in male Sprague-Dawley rats. Talinolol, a nonmetabolized P-gp substrate, was used as a marker compound. The white grapefruit juice (GFJ) had a minor effect on talinolol pharmacokinetics, but the ruby red GFJ reduced the C max and the AUC (0-infinity) by 60% and 50% of the control, respectively. However, among the GFJ constituents tested, bergamottin (0.22 mg/kg) was the most potent component augmenting the C max and the AUC (0-infinity) of talinolol by 2.4- and 1.8-fold, respectively, if compared to the control group. The flavonoids naringenin (0.7 mg/kg) and naringin (2.4 and 9.4 mg/kg) had a similar effect increasing the talinolol C max and AUC (0-infinity) by 1.5- to 1.8-fold, respectively. In conclusion, the effect of GFJ on P-gp activity seems to depend on the variety, the concentration of compounds in the juice, and the composition of different ingredients.
de Castro
Whocely Victor
WV
Department of Pharmaceutics, College of Pharmacy, University of Florida, 1600 SW Archer Road, P.O. Box 100494, Gainesville, FL 32610, USA.
Mertens-Talcott
Susanne
S
Derendorf
Hartmut
H
Butterweck
Veronika
V
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D001628:Beverages / Q000032:analysis; D001692:Biological Transport / Q000187:drug effects; D032083:Citrus paradisi / Q000737:chemistry*; D044950:Flavanones / Q000494:pharmacology*; D005638:Fruit / Q000737:chemistry; D011564:Furocoumarins / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D011412:Propanolamines / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D044950:Flavanones; D011564:Furocoumarins; D011412:Propanolamines; C011550:talinolol; C005273:naringenin; C068337:bergamottin; C005274:naringin