title: The use of heat treatment to eliminate drug interactions due to grapefruit juice.
abstract: Grapefruit juice (GJ) contains components that may increase the bioavailability of drugs; however, approaches to the removal of these components have been little investigated. It is known that furanocoumarin derivatives (FCs), such as bergamottin (BG) and 6',7'-dihydroxybergamottin (DHB) in GJ, induce such drug interactions. In the present study, it was found that the heat treatment of grapefruit juice decreases concentrations of BG and DHB as well as their interactions both in vitro and in vivo. We incubated GJ for 10, 20, 30, 40, 50, and 60 min at 37, 62, 72, and 95 degrees C; FCs in each sample were then measured, using high-performance liquid chromatography (HPLC). The concentrations of BG and DHB were decreased in a time- and temperature-dependent manner, by 82.5 and 97.9% respectively, after incubation for 1 h at 95 degrees C. In contrast, the concentration of bergaptrol (BT) increased in a time- and temperature-dependent manner (27.7% after 60 min at 95 degrees C). In addition, the effect of each GJ sample on testosterone 6beta-oxidation in human liver microsomes was observed. The inhibitory effects of GJ heated to 95 degrees C were decreased in a time-dependent manner, as in the case of BG and DHB concentrations. Furthermore, 2 ml of GJ treated for 60 min at 95 degrees C was administered into the rat duodenum. After 30 min, nifedipine (NFP) was administered intraduodenally at a dose of 3 mg/kg body weight. The concentrations of NFP in the plasma samples were determined by HPLC. No significant increase in the AUC of NFP was observed in the rats given heat-treated GJ. These results suggest that the heat treatment of GJ reduces the concentrations of FCs, thus eliminating the potential for drug interactions.
authors.affiliation: Clinical Pharmaceutics Laboratory, Department of Pharmaceutics, Meiji Pharmaceutical University, Kiyose, Japan. uesawa@my-pharm.ac.jp
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Uesawa
authors.forename: Kiminori
authors.initials: K
authors.lastname: Mohri
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001628:Beverages / Q000032:analysis*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D032083:Citrus paradisi; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D065692:Cytochrome P-450 CYP3A Inhibitors; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism; D018565:Food-Drug Interactions; D011564:Furocoumarins / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology; D006358:Hot Temperature; D006915:Hydroxytestosterones / Q000032:analysis / Q000378:metabolism; D007441:Intubation, Gastrointestinal; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D009543:Nifedipine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D002121:Calcium Channel Blockers; D065692:Cytochrome P-450 CYP3A Inhibitors; D011564:Furocoumarins; D006915:Hydroxytestosterones; C025591:6 beta-hydroxytestosterone; D051544:Cytochrome P-450 CYP3A; D009543:Nifedipine; C068337:bergamottin; C080771:bergaptol; C104774:6',7'-dihydroxybergamottin