Azanza José Ramón, García-Quetglas Emilio, Sádaba Belén
Servicio de Farmacología Clínica, Clínica Universitaria de Navarra, Facultad de Medicina Universidad de Navarra, Pamplona, Navarra, Spain.
Rev Iberoam Micol. 2007 Sep 30;24(3):223-7. doi: 10.1016/s1130-1406(07)70047-5.
Azole antifungals have different pharmacokinetic characteristics: complete oral absorption for Voriconazole, and to a lesser extent for fluconazole. The absorption of posaconazole and itraconazole increases with food intake. All of them have high tissue distribution with low plasma concentrations, especially low in the case of posaconazole and itraconazole. Posaconazole and itraconazole have high plasmatic protein binding and consequently both have a very low free fraction. Elimination of azole antifungals is through a metabolic pathway with CYP450 isoenzymes, and has a non linear pharmacokinetics with a high risk of interation with other drugs since azoles have the ability of CYP450 isoenzymes inhibition. Possibly the parameter that defines more precisely their efficacy is AUIC with an optimum value near 20, although cut-off values must be defined since some azoles may have difficulty to reach this value.
伏立康唑口服吸收完全,氟康唑的口服吸收程度稍低。泊沙康唑和伊曲康唑的吸收随食物摄入而增加。它们在组织中的分布均较高,血浆浓度较低,尤其是泊沙康唑和伊曲康唑的血浆浓度更低。泊沙康唑和伊曲康唑与血浆蛋白的结合率较高,因此二者的游离分数都非常低。唑类抗真菌药通过细胞色素P450同工酶代谢途径消除,具有非线性药代动力学,与其他药物相互作用的风险较高,因为唑类具有抑制细胞色素P450同工酶的能力。可能更精确地定义其疗效的参数是药时曲线下面积与血药浓度的乘积(AUIC),最佳值接近20,不过由于某些唑类可能难以达到该值,因此必须确定临界值。