In vitro inhibition of simvastatin metabolism, a HMG-CoA reductase inhibitor in human and rat liver by bergamottin, a component of grapefruit juice

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• 作者：Le Goff-Klein ; Nathalie ; Koffel ; Jean-Claude ; Jung ; Louis ; Ubeaud ; Geneviè ; ve
• 关键词：Simvastatin ; Grapefruit juice ; Naringenin ; Bergamottin ; CYP 450 ; Metabolism ; Inhibition ; BG ; bergamottin ; CYP 450 ; cytochrome P450 ; HMG-CoA ; 3-hydroxy-3-methylglutaryl coenzyme A ; K_i ; inhibition constant ; LC&ndash ; UV ; liquid chromatography&ndas
• 刊名：European Journal of Pharmaceutical Sciences
• 出版年：2003
• 出版时间：January, 2003
• 年：2003
• 卷：18
• 期：1
• 页码：31-35
• 全文大小：250 K

文摘

Grapefruit juice is responsible for many drug interactions but the exact components involved in this interaction are not precisely known. Flavonoids and furocoumarin derivatives such as naringenin and bergamottin, respectively, could be involved in the inhibition of drug metabolism. The objective of this paper is to investigate in vitro the possible metabolic hepatic interaction between simvastatin (SV) and bergamottin (BG) and thus to compare its effects to those of naringenin (NRG) the aglycone form of naringin (NR) (a flavonoid present in grapefruit juice). In human and rat microsomes and in rat hepatocytes, BG was found to be a mixed type inhibitor of SV metabolism. In rat liver microsomes the K_i value of BG (K_i