Department of Clinical Pharmacy, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Ther Drug Monit. 2012 Jun;34(3):320-5. doi: 10.1097/FTD.0b013e31824d135c.
Posaconazole is indicated for prophylaxis and salvage therapy of invasive fungal infections. Based on pharmacokinetic-pharmacodynamic data, minimum serum concentrations for each indication have been proposed, for example, for prophylaxis >0.5-0.7 mg/L and for primary therapy >1.0 mg/L. Several drugs and comorbidities have been identified to hinder reaching target concentrations. It is postulated that patients with interacting drugs or comorbidities should be monitored for posaconazole concentrations.
Patients aged 18 years and above were included for retrospective analysis if at least 1 serum posaconazole concentration was measured in our hospital between June 2009 and May 2010. Serum posaconazole concentrations were measured using a validated liquid chromatographic method with tandem mass-spectrometric analytical method. Patient characteristics, underlying disease, comedication, comorbidities, and therapeutic drug monitoring (TDM) interventions were collected retrospectively, based on (electronic) medical records.
Seventeen patients were included, from whom 42 samples for posaconazole measurement were collected. In total, 8 patients did not reach adequate posaconazole concentration. Sixty percent of patients using a proton pump inhibitor (PPI) did not reach target concentration with a corresponding median concentration of 0.48 mg/L. PPI usage was shown to significantly increase the risk of attaining below-target serum posaconazole concentration (P = 0.04 for all measurements). Graft-versus-host disease and diarrhea were associated with significant below-target concentrations (P = 0.03 and P < 0.001, respectively, for all measurements). One patient developed a breakthrough pulmonary aspergillosis at low posaconazole concentration (0.37 mg/L). Two patients had high concentrations (>3 mg/L), without adverse events. After TDM intervention, 3 out of 4 patients (75%) reached target concentration by spreading the administration of the dose.
Below-target posaconazole concentrations were significantly more frequent in PPI users, graft-versus-host disease, and diarrhea. TDM seemed to be a helpful tool to identify low concentrations and to optimize posaconazole treatment.
泊沙康唑用于预防和治疗侵袭性真菌感染。基于药代动力学-药效学数据，为每个适应证提出了最低血清浓度，例如，预防用 >0.5-0.7mg/L，一线治疗用 >1.0mg/L。已确定几种药物和合并症会阻碍达到目标浓度。有人推测，应监测合用药物或合并症的患者的泊沙康唑浓度。
如果 2009 年 6 月至 2010 年 5 月期间在我院至少测量过 1 次泊沙康唑血清浓度，我们将回顾性分析年龄≥18 岁的患者。采用经验证的液相色谱-串联质谱分析方法测量血清泊沙康唑浓度。根据（电子）病历，回顾性收集患者特征、基础疾病、合并用药、合并症和治疗药物监测（TDM）干预措施。
共纳入 17 例患者，共采集 42 个泊沙康唑样本。共有 8 例患者未达到足够的泊沙康唑浓度。80%使用质子泵抑制剂（PPI）的患者未达到目标浓度，相应的中位数浓度为 0.48mg/L。PPI 的使用显著增加了血清泊沙康唑浓度低于目标值的风险（所有测量值的 P=0.04）。移植物抗宿主病和腹泻与明显低于目标值的浓度相关（所有测量值的 P=0.03 和 P<0.001）。1 例患者在低泊沙康唑浓度（0.37mg/L）时发生突破性肺曲霉病。2 例患者浓度较高（>3mg/L），但无不良反应。经 TDM 干预后，4 例患者中的 3 例（75%）通过延长剂量给药时间达到了目标浓度。
PPI 使用者、移植物抗宿主病和腹泻患者的泊沙康唑浓度显著低于目标值。TDM 似乎是一种有用的工具，可以识别低浓度并优化泊沙康唑治疗。
