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[危重症患者的药物相互作用。米卡芬净使用中的一个重要因素?]

[Drug interactions in critically-ill patients. An important factor in the use of micafungin?].

作者信息

Garnacho-Montero José, Jiménez Parrilla Francisco

机构信息

Unidad Clínica de Cuidados Críticos y Urgencias, Unidad de Cuidados Intensivos, Hospital Universitario Virgen del Rocío, Sevilla, España.

出版信息

Enferm Infecc Microbiol Clin. 2011 Mar;29 Suppl 2:33-7. doi: 10.1016/S0213-005X(11)70007-6.

Abstract

Currently there are three main drug groups for the prevention and treatment of fungal infections: polyenes (amphotericin B deoxycholate or its lipid formulations), azoles (fluconazole, itraconazole or posaconazole) and echinocandins (caspofungin, micafungin and anidulafungin). However, a major characteristic to be evaluated when choosing an antifungal agent -apart from antifungal spectrum, pharmacokinetics and adverse effects- is the absence of significant drug interactions. Amphotericin B lacks interactions but may cause renal dysfunction, leading to the accumulation of renally metabolized drugs. Nephrotoxicity is significantly lower with lipid formulations, especially with liposomal amphotericin B. Azoles modify the metabolism of a wide range of drugs by inhibiting their biotransformation or altering their distribution and elimination. These drugs are metabolized in the liver through the P450 cytochrome complex, inhibiting several isoenzymes, especially CYP3A4, the main drug-metabolizing enzyme. Moreover, itraconazole and posaconazole are substrates and inhibitors of the transporter protein, P-glycoprotein. Fluconazole is the azole with the fewest drug-drug interactions. The echinocandins have increased the therapeutic arsenal and a particular feature of these drugs is their safety, due to the absence of severe adverse effects and the scarce number of interactions. The echinocandin with the highest number of interactions is caspofungin. Micafungin is an echinocandin lacking in relevant interactions and consequently its dosage requires no adjustment in any of its indications. This drug can be used both in adults and in the pediatric population, including neonates.

摘要

目前有三类主要药物用于预防和治疗真菌感染

多烯类(去氧胆酸盐两性霉素B或其脂质制剂)、唑类(氟康唑、伊曲康唑或泊沙康唑)和棘白菌素类(卡泊芬净、米卡芬净和阿尼芬净)。然而,在选择抗真菌药物时,除了抗真菌谱、药代动力学和不良反应外,另一个需要评估的主要特性是不存在显著的药物相互作用。两性霉素B没有药物相互作用,但可能导致肾功能不全,从而导致经肾脏代谢的药物蓄积。脂质制剂的肾毒性显著降低,尤其是脂质体两性霉素B。唑类通过抑制药物的生物转化或改变其分布和消除来改变多种药物的代谢。这些药物在肝脏中通过细胞色素P450复合物代谢,抑制几种同工酶,尤其是主要的药物代谢酶CYP3A4。此外,伊曲康唑和泊沙康唑是转运蛋白P-糖蛋白的底物和抑制剂。氟康唑是药物相互作用最少的唑类。棘白菌素类增加了治疗手段,这些药物的一个特别之处在于其安全性,因为它们没有严重的不良反应且相互作用较少。相互作用最多的棘白菌素是卡泊芬净。米卡芬净是一种没有相关相互作用的棘白菌素,因此在其任何适应症中都无需调整剂量。这种药物可用于成人和儿童人群,包括新生儿。

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