Department of Microbiology and Infectious Disease, Royal Prince Alfred Hospital, Sydney, Australia.
Institute of Haematology, Royal Prince Alfred Hospital, Sydney, Australia.
J Antimicrob Chemother. 2019 Oct 1;74(10):3049-3055. doi: 10.1093/jac/dkz303.
SUper BioAvailability-itraconazole (SUBA®-itraconazole) was introduced into Australia in April 2014 as a substitute for standard itraconazole on the basis of improved bioavailability, tolerance and interpatient variability. Shortly after its introduction, our centre converted to the novel formulation for mould prophylaxis in patients undergoing allogeneic HSCT, autologous HSCT or treatment for haematological malignancies with an intermediate/high risk of invasive fungal infection (IFI).
A single-institution, investigator-initiated retrospective cohort study was conducted between June 2016 and April 2018 to assess therapeutic drug concentrations, safety and tolerability of a standard prophylactic dose of SUBA®-itraconazole.
A total of 74 patients were assessed across 98 admissions with 178 measured itraconazole trough concentrations. The median duration of prophylaxis was 15.5 (1-59) days. No significant correlation was identified between trough concentrations and patient demographics including gender and weight. Drug concentrations were reduced by gastric acid suppression and diarrhoea. Therapeutic itraconazole trough concentrations (≥0.5 mg/L) were achieved at a median of 7 (95% CI = 6-8) days, with 87% of patients achieving therapeutic concentrations at day 14 (expected steady-state). One (1%) proven/probable IFI and 5 (5%) possible breakthrough IFIs were identified. Although adverse events were experienced by 42% of the cohort, only a single event was directly attributable to SUBA®-itraconazole, resulting in change of prophylactic agent.
SUBA®-itraconazole achieved rapid therapeutic trough concentrations, was associated with low rates of IFI and was well tolerated in the study population. This formulation should be considered a realistic and safe first-line agent for the prevention of IFIs in those undergoing HSCT and intermediate/high-risk therapy for haematological malignancies.
超生物利用度伊曲康唑（SUBA®-伊曲康唑）于 2014 年 4 月在澳大利亚推出，作为标准伊曲康唑的替代品，具有更好的生物利用度、耐受性和患者间变异性。在推出后不久，我们中心将其新型制剂转换为用于同种异体 HSCT、自体 HSCT 或接受中间/高危侵袭性真菌感染（IFI）治疗的血液恶性肿瘤患者的新型制剂。
我们进行了一项单中心、研究者发起的回顾性队列研究，旨在评估标准预防剂量的 SUBA®-伊曲康唑的治疗药物浓度、安全性和耐受性。
共有 74 例患者在 98 次住院期间接受了评估，共测量了 178 次伊曲康唑谷浓度。预防的中位持续时间为 15.5（1-59）天。未发现谷浓度与患者人口统计学特征（包括性别和体重）之间存在显著相关性。胃酸抑制和腹泻会降低药物浓度。达到治疗性伊曲康唑谷浓度（≥0.5mg/L）的中位时间为 7 天（95%CI = 6-8），87%的患者在第 14 天（预期稳态）达到治疗浓度。确定了 1 例（1%）确诊/可能的 IFI 和 5 例（5%）可能的突破 IFI。尽管该队列中有 42%的患者经历了不良事件，但只有 1 例直接归因于 SUBA®-伊曲康唑，导致预防性药物改变。
SUBA®-伊曲康唑迅速达到治疗谷浓度，与低 IFI 发生率相关，在研究人群中具有良好的耐受性。在接受 HSCT 和中间/高危血液恶性肿瘤治疗的患者中，这种制剂应被视为预防 IFI 的现实且安全的一线药物。
