Baltes M R, Dubois J G, Hanocq M
Université Libre de Bruxelles, Institut de Pharmacie, Laboratoire de Chimie Bioanalytique, Toxicologie et Chimie Physique Appliquée, Campus de la Plaine, Boulevard du Triomphe, CP 205/01, 1050 Brussels, Belgium.
Talanta. 2001 Jun 21;54(5):983-7. doi: 10.1016/s0039-9140(01)00368-x.
Classical inhibitors of human cytochrome P450 3A4 activity, such as ketoconazol and quercetin, are tested to prove the efficiency of a new metabolisation model using living entire cells. Grapefruit juice is a well-known potent inhibitor of cytochrome P450 3A4 activity. With regard to the clinical relevance of grapefruit juice-drug interactions, an investigation of other common juices is undertaken with this in vitro model. The CYP3A4 activity is measured by the formation of the 6beta-hydroxytestosterone, which is quantified by an isocratic high performance liquid chromatography. It is demonstrated for the first time that lemon juice significantly inhibits by 60+/-3% the CYP3A4-mediated oxidation. Grapefruit juice inhibits this activity by 82+/-4%. The mechanism of lemon juice inhibition is competitive, whereas it is mixed for grapefruit juice. These results suggest that our in vitro model combined with our analytical method is applicable for the investigation of the inhibition of CYP3A4 not only by chemical inhibitors but also by natural food products.
对人类细胞色素P450 3A4活性的经典抑制剂，如酮康唑和槲皮素进行了测试，以验证使用完整活细胞的新代谢模型的有效性。葡萄柚汁是一种众所周知的细胞色素P450 3A4活性强效抑制剂。鉴于葡萄柚汁与药物相互作用的临床相关性，利用该体外模型对其他常见果汁进行了研究。通过6β-羟基睾酮的形成来测定CYP3A4活性，该物质通过等度高效液相色谱法定量。首次证明柠檬汁可显著抑制CYP3A4介导的氧化，抑制率为60±3%。葡萄柚汁对该活性的抑制率为82±4%。柠檬汁的抑制机制是竞争性的，而葡萄柚汁的抑制机制是混合型的。这些结果表明，我们的体外模型与分析方法不仅适用于研究化学抑制剂对CYP3A4的抑制作用，也适用于研究天然食品对其的抑制作用。
