Processing grapefruit juice with γ‐cyclodextrin attenuates its inhibitory effect on cytochrome P450 3A activity. (11th December 2019)

• Record Type: Journal Article
• Authors: Yamasaki, Keishi; Iohara, Daisuke; Oyama, Yoko; Nishizaki, Narumi; Kawazu, Seitaro; Nishi, Koji; Kadowaki, Daisuke; Taguchi, Kazuaki; Otagiri, Masaki; Seo, Hakaru
• Is Part Of: Journal of pharmacy and pharmacology. Volume 72:Number 3(2020)
• Page Start: 356
• Page End: 363
• Publication Date: 2019-12-11
• Subjects: grapefruit juice -- cyclodextrins -- cytochrome P450 -- drug interaction; Pharmacy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/jphp.13212
• Languages: English
• ISSNs: 0022-3573

Abstract

Abstract: Objectives: Grapefruit ( Citrus paradisi ) juice enhances the oral bioavailability of drugs that are metabolized by intestinal cytochrome P450 3A4 (CYP3A4). Patients are advised to avoid drinking grapefruit juice to prevent this drug–grapefruit juice interaction. The aim of this study was to investigate whether processing grapefruit juice with cyclodextrins (CDs) would result in preventing or inhibiting this interaction. Methods: Grapefruit juice and the major furanocoumarins found in grapefruit, bergamottin (BG) and 6′, 7′‐dihydroxy bergamottin (DHBG) were mixed with α, β and γCDs. The effects of these processed juice samples and furanocoumarins on CYP3A activity were compared with the corresponding values for unprocessed juices and furanocoumarins. Interactions between CDs and these furanocoumarins were also investigated by phase solubility and 1 H NMR studies. Key findings: The inhibition of CYP3A by grapefruit juice was significantly attenuated by processing particularly with γCD. Similar attenuation effects by γCD were observed in the cases of BG and DHBG. Furthermore, BG and DHBG were suggested to be strongly encapsulated in the cavity of γCD. Conclusion: The encapsulation of BG and DHBG by γCD and the resulting attenuation of the inhibition of CYP3A activity by grapefruit juice may be applicable to juice processing for preventing drug‐grapefruit juice interactions.