Nivoix Yasmine, Levêque Dominique, Herbrecht Raoul, Koffel Jean-Claude, Beretz Laurence, Ubeaud-Sequier Genevieve
Pôle Pharmacie-Pharmacologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
Clin Pharmacokinet. 2008;47(12):779-92. doi: 10.2165/0003088-200847120-00003.
Drug-drug interactions are a recurring problem in immunocompromised patients treated with triazole antifungals. While the introduction of new antifungals has expanded opportunities for lowering drug toxicity, virtually all antifungal regimens carry the risk of pharmacokinetic and pharmacodynamic interaction. This review presents the published data on molecular determinants (enzymes, transporters, orphan nuclear receptors) of systemic triazole pharmacokinetics in humans, including itraconazole, fluconazole, voriconazole and posaconazole. Systemic triazoles are inhibitors of cytochrome P450 (CYP) isozymes, such as CYP3A4, CYP2C9 and CYP2C19, to varying degrees. In addition, some are substrates and/or inhibitors of drug transporters such as multidrug resistance-1 gene product, P-glycoprotein, or breast cancer resistance protein. The interactions of triazole antifungals can be divided into the following categories: modifications of antifungal pharmacokinetics by other drugs, modifications of other drug pharmacokinetics by antifungals, and two-way interactions. These features are the basis of most interactions that occur during triazole therapy.
在接受三唑类抗真菌药物治疗的免疫功能低下患者中,药物相互作用是一个反复出现的问题。虽然新型抗真菌药物的引入为降低药物毒性提供了更多机会,但几乎所有抗真菌治疗方案都存在药代动力学和药效学相互作用的风险。本综述介绍了已发表的关于人类全身性三唑类药代动力学分子决定因素(酶、转运体、孤儿核受体)的数据,包括伊曲康唑、氟康唑、伏立康唑和泊沙康唑。全身性三唑类药物在不同程度上是细胞色素P450(CYP)同工酶的抑制剂,如CYP3A4、CYP2C9和CYP2C19。此外,一些药物还是药物转运体的底物和/或抑制剂,如多药耐药-1基因产物、P-糖蛋白或乳腺癌耐药蛋白。三唑类抗真菌药物的相互作用可分为以下几类:其他药物对抗真菌药代动力学的影响、抗真菌药物对其他药物药代动力学的影响以及双向相互作用。这些特性是三唑类治疗期间发生的大多数相互作用的基础。