Bergamottin contribution to the grapefruit juice?felodipine interaction and disposition in humans

Goosen, Theunis C.; CILLIE, D; Bailey, David G.; Yu, Cheng Der; He, Kan; Hollenberg, Paul F.; Woster, Patrick M.; Cohen, Lee M.; Ja, Williams; Rheeders, Malie

doi:10.1016/j.clpt.2004.08.019

Cited by 77 publications

(58 citation statements)

References 40 publications

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“…ϩ2 for this modified peptide can be identified in the MS/MS spectrum. The mass increase of 388 Da observed in the b2 to b10 ions, whereas the lack of any mass increase in the y3 through y9 ions observed in the modified peptide, indicates that Gln273 is the amino acid residue modified by a reactive intermediate of DHBG, which is a metabolite of BG (Goosen et al, 2004;Kent et al, 2006).…”

Section: Lc-ms/ms Analysis Of the Gsh Conjugates Formed During Metabomentioning

confidence: 99%

“…Subsequently, studies in primary cultured hepatocytes and more clinically related research with BG and DHBG were pursued (Wen et al, 2002;Goosen et al, 2004;Kakar et al, 2004;Paine et al, 2004Paine et al, , 2006. Accelerated degradation of CYP3A4 after covalent modification of the apoprotein by BG and DHBG was confirmed to play a role in the grapefruit juice effect by several in vivo studies (Goosen et al, 2004;Kakar et al, 2004;Paine et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

“…Bergamottin (BG) and 6Ј,7Ј-dihydroxybergamottin (DHBG), the two most abundant furanocoumarins present in grapefruit, have been characterized as reversible inhibitors and as mechanism-based inactivators of CYP3A4 (Schmiedlin-Ren et al, 1997;He et al, 1998;Guo et al, 2000;Ohnishi et al, 2000;Tassaneeyakul et al, 2000). Subsequently, studies in primary cultured hepatocytes and more clinically related research with BG and DHBG were pursued (Wen et al, 2002;Goosen et al, 2004;Kakar et al, 2004;Paine et al, 2004Paine et al, , 2006. Accelerated degradation of CYP3A4 after covalent modification of the apoprotein by BG and DHBG was confirmed to play a role in the grapefruit juice effect by several in vivo studies (Goosen et al, 2004;Kakar et al, 2004;Paine et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

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Identification of the Residue in Human CYP3A4 That Is Covalently Modified by Bergamottin and the Reactive Intermediate That Contributes to the Grapefruit Juice Effect

Lin¹,

Kenaan²,

Hollenberg³

2012

Drug Metab Dispos

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Section: Lc-ms/ms Analysis Of the Gsh Conjugates Formed During Metabomentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Identification of the Residue in Human CYP3A4 That Is Covalently Modified by Bergamottin and the Reactive Intermediate That Contributes to the Grapefruit Juice Effect

Lin¹,

Kenaan²,

Hollenberg³

2012

Drug Metab Dispos

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“…[5][6][7][8][9][10][11] Therefore FCs in GJ used in this investigation were determined comprehensively by the HPLC system with a photodiode array detector. As a result, three kinds of FCs-BG, DHB, and BT-were detected; 17.9, 7.85, and 50.7 mM, respectively (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Furanocoumarin derivatives (FCs), such as bergamottin (BG) and 6Ј,7Ј-dihydroxybergamottin (DHB), in GJ inhibit this process. [5][6][7][8][9][10][11] Therefore, in order to produce GJ that vulnerable patients may drink, it would be useful to remove the interactive components of GJ. This possibility has been little investigated.…”

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confidence: 99%

The Use of Heat Treatment to Eliminate Drug Interactions Due to Grapefruit Juice

Uesawa

Mohri

2006

Biological & Pharmaceutical Bulletin

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It has been reported that when many types of drugs, including dihydropyridine calcium antagonists, are taken with grapefruit juice (GJ), their concentrations in plasma increases due to their increased bioavailabilities.1,2) Serious adverse effects have been known to result. 3,4) Many patients being treated for chronic diseases are forbidden to drink GJ for the rest of their lives because of the risk of such drug interactions. The drugs interacting with GJ are metabolized by CYP3A enzymes in the small intestine. Furanocoumarin derivatives (FCs), such as bergamottin (BG) and 6Ј,7Ј-dihydroxybergamottin (DHB), in GJ inhibit this process. [5][6][7][8][9][10][11] Therefore, in order to produce GJ that vulnerable patients may drink, it would be useful to remove the interactive components of GJ. This possibility has been little investigated.We recently reported that ultraviolet (UV) irradiation eliminates FCs in GJ.12) Furthermore, GJ that was UV-irradiated for 6 h lost the ability to interact with intraduodenal nifedipine (NFP) in rats. However, this method has the drawback that, over the long term, toxic substances might be formed in UV-irradiated GJ. Paine et al. have reported a method of removing BG and DHB from GJ by means of a pilot-scale citrus-debittering system consisting of three ultrafiltration cartridges and a styrene divinyl benzene absorption resin system.13) This equipment is complicated and probably expensive. In the present study, we found that BG and DHB in GJ were unstable at high temperatures. It is therefore proposed that the heat treatment of GJ might serve as the basis for the removal of interactive FCs and thus the elimination of potential drug interactions. Furthermore, GJ samples after heat treatment under various conditions, including various concentrations of FCs, are still useful for elucidating the functions of FCs in drug interactions. With such a background, we studied the effect of incubation at various temperatures on the concentrations of FCs in GJ, and the actions of the GJ samples on the drug interactions in vitro and in vivo. MATERIALS AND METHODSAll handling procedures involving NFP and nitrendipine were performed under subdued light.Materials Anthracene [internal standard (IS)] was obtained from Wako Pure Chemical Industries Ltd. (Osaka, Japan). BG and DHB were purchased from Daiichi Pure Chemicals Co., Ltd. (Tokyo, Japan). Bergaptol (BT) was obtained from Funakoshi Co., Ltd. (Tokyo, Japan). NFP was purchased from Wako Pure Chemical Industries. Nitrendipine [internal standard (IS2)] was obtained from Yoshitomi Pharmaceutical Industries, Ltd. (Osaka, Japan). Testosterone was obtained from Nacalai Tesque, Inc. (Kyoto, Japan). 6b-Hydroxytestosterone and corticosterone [internal standard (IS3)] were purchased from Daiichi Pure Chemicals and Wako Pure Chemical Industries, respectively. Pooled human hepatic microsomes were obtained from BD Biosciences (San Jose, CA, U.S.A.). Methanol, acetonitrile, and phosphoric acid of HPLC grade were used (Wako). All other chemicals were of reagent g...

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Xenobiotic Metabolism

Ioannides¹

2008

Wiley Encyclopedia of Chemical Biology

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Humans are exposed continuously and unavoidably to a myriad of potentially toxic chemicals that are inherently lipophilic and, consequently, very difficult to excrete. To effect their elimination, the human body has developed appropriate enzyme systems that can transform metabolically these chemicals to hydrophilic, readily excretable, metabolites. This biotransformation process occurs in two distinct phases, Phase I and Phase II, and involves several enzyme systems, the most important being the cytochromes P450. The expression of these enzyme systems is regulated genetically but can be modulated also other factors, such as exposure to chemicals that can either increase or impair activity. Paradoxically, the same xenobiotic‐metabolizing enzyme systems also can convert biologically inactive chemicals to highly reactive intermediates that interact with vital cellular macromolecules and elicit various forms of toxicity. Thus, xenobiotic metabolism does not always lead to deactivation but can result also in metabolic activation with deleterious consequences.

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Bergamottin contribution to the grapefruit juice?felodipine interaction and disposition in humans

Cited by 77 publications

References 40 publications

Identification of the Residue in Human CYP3A4 That Is Covalently Modified by Bergamottin and the Reactive Intermediate That Contributes to the Grapefruit Juice Effect

Identification of the Residue in Human CYP3A4 That Is Covalently Modified by Bergamottin and the Reactive Intermediate That Contributes to the Grapefruit Juice Effect

The Use of Heat Treatment to Eliminate Drug Interactions Due to Grapefruit Juice

Xenobiotic Metabolism

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