Cojutti Piergiorgio, Candoni Anna, Simeone Erica, Franceschi Loretta, Fanin Renato, Pea Federico
Institute of Clinical Pharmacology, Azienda Ospedaliero-Universitaria Santa Maria della Misericordia, Department of Experimental and Clinical Medical Sciences, University of Udine, Udine, Italy.
Antimicrob Agents Chemother. 2013 Dec;57(12):6081-4. doi: 10.1128/AAC.01586-13. Epub 2013 Sep 23.
This study aimed to assess the influence of dose frequency and the presence or absence of cotreatment with proton pump inhibitors (PPIs) on the time to a target trough concentration (Cmin) of >700 ng/ml with posaconazole in the first 8 days of antifungal prophylaxis in hematological patients. This was a retrospective, observational study performed with 42 adult patients with acute myeloid leukemia who underwent posaconazole prophylaxis with 200 mg every 8 h (q8h) or 200 mg q6h after receiving induction chemotherapy and who had at least three subsequent therapeutic drug monitoring assessments during the first 8 days of treatment. The cohort was split into four groups (group 1, 200 mg q8h without PPI; group 2, 200 mg q8h with PPI; group 3, 200 mg q6h without PPI; group 4, 200 mg q6h with PPI). Rapid attainment of the target Cmin was obtained only in group 3 (P < 0.01) (median Cmin on day 4 of 935.5 ng/ml [interquartile range, 760.0 to 1,270.0 ng/ml] in group 3, versus 567.0 ng/ml [346 to 906 ng/ml] in group 1, 420.0 ng/ml [326.2 to 527.2 ng/ml] in group 2, and 514.0 ng/ml [403.7 to 564.7 ng/ml] in group 4). A linear accumulation of posaconazole over time was observed among patients in groups 1 and 3, regardless of the total daily dosage, differently from what occurred among those receiving PPI cotreatment (groups 2 and 4). Dose intensification (200 mg q6h) coupled with avoidance of PPI coadministration may represent a very powerful strategy to rapidly achieve effective concentrations with posaconazole in neutropenic hematological patients.
本研究旨在评估给药频率以及是否联合使用质子泵抑制剂（PPI）对血液学患者抗真菌预防治疗前8天泊沙康唑达到>700 ng/ml目标谷浓度（Cmin）所需时间的影响。这是一项回顾性观察研究，对42例成年急性髓系白血病患者进行，这些患者在接受诱导化疗后每8小时（q8h）或每6小时（q6h）接受200 mg泊沙康唑预防治疗，且在治疗的前8天至少进行了三次后续治疗药物监测评估。该队列被分为四组（第1组，每8小时200 mg，不联用PPI；第2组，每8小时200 mg，联用PPI；第3组，每6小时200 mg，不联用PPI；第4组，每6小时200 mg，联用PPI）。仅第3组快速达到了目标Cmin（P<0.01）（第3组第4天的中位Cmin为935.5 ng/ml[四分位间距，760.0至1270.0 ng/ml]，而第1组为567.0 ng/ml[346至906 ng/ml]，第2组为420.0 ng/ml[326.2至527.2 ng/ml]，第4组为514.0 ng/ml[403.7至564.7 ng/ml]）。第1组和第3组患者中，无论每日总剂量如何，均观察到泊沙康唑随时间呈线性蓄积，这与接受PPI联合治疗的患者（第2组和第4组）不同。剂量强化治疗（每6小时200 mg）并避免联用PPI可能是使中性粒细胞减少的血液学患者快速达到泊沙康唑有效浓度的一种非常有效的策略。
