Ullmann A J, Cornely O A, Burchardt A, Hachem R, Kontoyiannis D P, Töpelt K, Courtney R, Wexler D, Krishna G, Martinho M, Corcoran G, Raad I
Third Medical Department, Johannes Gutenberg-University, Mainz, Germany.
Antimicrob Agents Chemother. 2006 Feb;50(2):658-66. doi: 10.1128/AAC.50.2.658-666.2006.
The pharmacokinetic profiles, safety, and efficacies of different dosing schedules of posaconazole oral suspension in patients with possible, probable, and proven refractory invasive fungal infection (rIFI) or febrile neutropenia (FN) were evaluated in a multicenter, open-label, parallel-group study. Sixty-six patients with FN and 32 patients with rIFI were randomly assigned to one of three posaconazole regimens: 200 mg four times a day (q.i.d.) for nine doses, followed by 400 mg twice a day (b.i.d.); 400 mg q.i.d. for nine doses, followed by 600 mg b.i.d.; or 800 mg b.i.d. for five doses, followed by 800 mg once a day (q.d.). Therapy was continued for up to 6 months in patients with rIFI or until neutrophil recovery occurred in patients with FN. The 400-mg-b.i.d. dose provided the highest overall mean exposure, with 135% (P = 0.0004) and 182% (P < 0.0001) greater exposure than the 600-mg-b.i.d. and 800-mg-q.d. doses, respectively. However, exposure in allogeneic bone marrow transplant (BMT) recipients (n = 12) was 52% lower than in non-BMT patients. Treatment-related adverse events (occurring in 24% of patients) were mostly gastrointestinal in nature. Twenty-four percent of patients had adverse events leading to premature discontinuation (none were treatment related). In efficacy-evaluable patients, successful clinical response was observed in 43% with rIFI (56% of patients receiving 400 mg b.i.d., 17% receiving 600 mg b.i.d., and 50% receiving 800 mg q.d.) and 77% with FN (74% receiving 400 mg b.i.d., 78% receiving 600 mg b.i.d., and 81% receiving 800 mg q.d.). Posaconazole is well tolerated and absorbed. Divided doses of 800 mg (400 mg b.i.d.) provide the greatest posaconazole exposure.
在一项多中心、开放标签、平行组研究中，评估了泊沙康唑口服混悬液不同给药方案在可能、很可能及确诊的难治性侵袭性真菌感染（rIFI）或发热性中性粒细胞减少症（FN）患者中的药代动力学特征、安全性和疗效。66例FN患者和32例rIFI患者被随机分配至三种泊沙康唑治疗方案之一：200mg每日4次（q.i.d.），共9剂，之后400mg每日2次（b.i.d.）；400mg q.i.d.，共9剂，之后600mg b.i.d.；或800mg b.i.d.，共5剂，之后800mg每日1次（q.d.）。rIFI患者治疗持续长达6个月，或FN患者直至中性粒细胞恢复。400mg b.i.d.剂量提供了最高的总体平均暴露量，分别比600mg b.i.d.和800mg q.d.剂量的暴露量高135%（P = 0. 0004）和182%（P < 0. 0001）。然而，异基因骨髓移植（BMT）受者（n = 12）的暴露量比非BMT患者低52%。与治疗相关的不良事件（24%的患者发生）大多为胃肠道性质。24%的患者发生导致提前停药的不良事件（均与治疗无关）。在可评估疗效的患者中，rIFI患者43%观察到成功的临床反应（接受400mg b.i.d.的患者中56%、接受600mg b.i.d.的患者中17%、接受800mg q.d.的患者中50%），FN患者77%观察到成功的临床反应（接受400mg b.i.d.的患者中74%、接受600mg b.i.d.的患者中78%、接受800mg q.d.的患者中81%）。泊沙康唑耐受性良好且吸收良好。800mg（400mg b.i.d.）的分次剂量提供了最大的泊沙康唑暴露量。
