Kane G C, Lipsky J J
Department of Internal Medicine, Mayo Clinic, Rochester, Minn. 55905, USA.
Mayo Clin Proc. 2000 Sep;75(9):933-42. doi: 10.4065/75.9.933.
Grapefruit juice, a beverage consumed in large quantities by the general population, is an inhibitor of the intestinal cytochrome P-450 3A4 system, which is responsible for the first-pass metabolism of many medications. Through the inhibition of this enzyme system, grapefruit juice interacts with a variety of medications, leading to elevation of their serum concentrations. Most notable are its effects on cyclosporine, some 1,4-dihydropyridine calcium antagonists, and some 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. In the case of some drugs, these increased drug concentrations have been associated with an increased frequency of dose-dependent adverse effects. The P-glycoprotein pump, located in the brush border of the intestinal wall, also transports many cytochrome P-450 3A4 substrates, and this transporter also may be affected by grapefruit juice. This review discusses the proposed mechanisms of action and the medications involved in drug-grapefruit juice interactions and addresses the clinical implications of these interactions.
葡萄柚汁是普通大众大量饮用的一种饮品，它是肠道细胞色素P-450 3A4系统的抑制剂，该系统负责许多药物的首过代谢。通过抑制这一酶系统，葡萄柚汁与多种药物相互作用，导致它们的血清浓度升高。最显著的是它对环孢素、一些1,4-二氢吡啶类钙拮抗剂以及一些3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂的影响。对于某些药物而言，这些升高的药物浓度与剂量依赖性不良反应的发生频率增加有关。位于肠壁刷状缘的P-糖蛋白泵也转运许多细胞色素P-450 3A4底物，并且这种转运蛋白也可能受到葡萄柚汁的影响。本文综述讨论了药物与葡萄柚汁相互作用的作用机制及相关药物，并阐述了这些相互作用的临床意义。
