Hummert Shelly E, Green Myke R
*Division of Pharmacy Services, Providence St. Vincent Medical Center, Portland, Oregon; †Division of Pharmacy Services, University of Arizona Medical Center; and ‡Section of Hematology/Oncology, University of Arizona Cancer Center, Tucson.
Ther Drug Monit. 2015 Aug;37(4):508-11. doi: 10.1097/FTD.0000000000000175.
Prophylaxis with posaconazole, an extended-spectrum triazole antifungal, has been shown to increase overall survival in adults with acute myeloid leukemia receiving intensive remission induction chemotherapy. A paucity of data exists evaluating therapeutic drug monitoring and subsequent dose adjustment based on serum concentrations in humans.
An observational study was performed in 29 adult patients with acute myeloid leukemia who initially received posaconazole oral suspension 200 mg 3 times daily and required ≥1 dose adjustment because of steady-state posaconazole serum concentration <0.7 mcg/mL. Four dosing schemas were compared simultaneously. Patient records were reviewed to collect patient-related and medication-related factors that may affect serum concentrations.
Thirty-five percent of patients experienced subtherapeutic posaconazole serum concentrations with prophylactic dosing of posaconazole oral suspension. Increasing the dose and/or schedule of posaconazole oral suspension led to attainment of goal posaconazole serum concentrations in all groups. However, patients who received 400 mg orally 3 times daily experienced the least significant increase in serum concentration and remained subtherapeutic, despite doubling the posaconazole daily dose. Toxicities were similar to baseline within all groups. Increasing the dose and/or frequency of posaconazole oral suspension led to an increase in systemic exposure and did not appreciably increase incidence of toxicities.
Patients receiving posaconazole oral suspension that experience subtherapeutic posaconazole serum concentrations may benefit from increasing the frequency to 200 mg orally 4 times daily or dose to 300 mg orally 3 times daily.
泊沙康唑是一种广谱三唑类抗真菌药物，预防性使用泊沙康唑已被证明可提高接受强化缓解诱导化疗的急性髓系白血病成年患者的总生存率。目前缺乏基于人体血清浓度评估治疗药物监测及后续剂量调整的数据。
对29例急性髓系白血病成年患者进行了一项观察性研究，这些患者最初接受每日3次、每次200mg的泊沙康唑口服混悬液治疗，且由于泊沙康唑稳态血清浓度<0.7μg/mL而需要≥1次剂量调整。同时比较了四种给药方案。回顾患者记录以收集可能影响血清浓度的患者相关和药物相关因素。
35%的患者在预防性使用泊沙康唑口服混悬液时出现泊沙康唑血清浓度低于治疗水平的情况。增加泊沙康唑口服混悬液的剂量和/或给药频率可使所有组达到泊沙康唑血清浓度目标。然而，每日口服3次、每次400mg的患者血清浓度升高最不显著，尽管泊沙康唑日剂量加倍，仍低于治疗水平。所有组的毒性与基线相似。增加泊沙康唑口服混悬液的剂量和/或频率导致全身暴露增加，但并未明显增加毒性发生率。
接受泊沙康唑口服混悬液治疗但泊沙康唑血清浓度低于治疗水平的患者，每日口服4次、每次200mg或每日口服3次、每次300mg可能有益。
