泊沙康唑药动学及其治疗药物监测方法研究进展

Advances research on pharmacokinetics and therapeutic drug monitoring of posaconazole

泊沙康唑作为第二代三唑类抗真菌药物,其抗菌谱广、抗菌作用强、耐受性好,因而受到临床广泛关注。泊沙康唑口服制剂达峰时间为3~5 h,血浆蛋白结合率高达98%,其体内药物代谢受食物、用药方案、药物相互作用等因素影响,导致个体间血浆药物浓度变异性大,而泊沙康唑血浆药物浓度与其临床疗效密切相关,故推荐临床开展泊沙康唑治疗药物监测,以保证其稳态谷浓度大于有效浓度。目前常用于泊沙康唑浓度检测的方法有微生物检定法、化学荧光法及色谱法,其中液相色谱串联质谱法灵敏、准确、简单,为药物浓度检测"金标准"。

As a second generation of triazole antifungal drug,posaconazole has been widely used in clinic because of its wide antibacterial spectrum,strong antimicrobial activity and good tolerance.The tmaxof posaconazole is 3—5 h,and the binding rate of plasma protein was up to 98%.However,the pharmacokinetics of posaconazole are easily affected by food,drug regimen,drug interaction and other factors,resulting in great variability of drug concentration in plasma among individuals,and drug concentration of posaconazole is closely related to its clinical efficacy.Therefore,it is recommended to carry out therapeutic drug monitoring of posaconazole.At present,the commonly used methods for the detection of posaconazole concentration include microbial assay,chemical fluorescence and chromatography.Among them,liquid chromatography tandem mass spectrometry is sensitive,accurate and simple,and is the"gold standard"for the detection of drug concentration.