Chan J D
School of Pharmacy, University of Washington, Seattle 98195, USA.
Pharmacotherapy. 1998 Nov-Dec;18(6):1304-7.
Involvement of the cytochrome P450 (CYP) 3A subfamily in the metabolism of vincristine is well established. However, information is limited regarding vincristine's drug interaction profile. All the substrates and inhibitors of CYP3A4 such as the azole antifungals (itraconazole, ketoconazole), cyclosporine, isoniazid, and nifedipine have very high propensity to interfere with vincristine metabolism. The proposed mechanism is most likely attributed to either inhibition of 3A4 enzymes or blockade of P-glycoprotein pumps. These interactions are clinically significant and can lead to severe vincristine toxicity if not detected. Although case reports discussed here exclusively involve vincristine, it is important to assume that all vinca alkaloids interact in the same manner until proved otherwise, because they share similar metabolism pathways.
细胞色素P450（CYP）3A亚家族参与长春新碱的代谢已得到充分证实。然而，关于长春新碱的药物相互作用情况，相关信息有限。CYP3A4的所有底物和抑制剂，如唑类抗真菌药（伊曲康唑、酮康唑）、环孢素、异烟肼和硝苯地平，都极有可能干扰长春新碱的代谢。推测其机制很可能是抑制3A4酶或阻断P-糖蛋白泵。这些相互作用具有临床意义，如果未被检测到，可能导致严重的长春新碱毒性。尽管此处讨论的病例报告仅涉及长春新碱，但在未得到其他证明之前，假定所有长春花生物碱都以相同方式相互作用很重要，因为它们具有相似的代谢途径。
