Service de Réanimation Médicale, Hôpital Pitié-Salpêtrière, Paris, France.
J Aerosol Med Pulm Drug Deliv. 2011 Aug;24(4):183-90. doi: 10.1089/jamp.2010.0860. Epub 2011 Mar 1.
BAY41-6551, a drug-device combination in development for adjunctive treatment of Gram-negative pneumonia in intubated and mechanically ventilated patients, consists of amikacin formulated for inhalation coupled with the Pulmonary Drug Delivery System (PDDS) Clinical aerosol delivery platform. Given the predominantly renal clearance of aminoglycosides, understanding systemic amikacin exposure and safety during administration of BAY41-6551 to patients with acute renal failure (ARF) is clinically important.
Seven mechanically ventilated patients with Gram-negative pneumonia and ARF receiving continuous veno-venous hemodiafiltration (CVVHDF) were treated with multiple administrations of BAY41-6551 400 mg amikacin twice daily using the PDDS Clinical on-ventilator device [in addition to standard intravenous (i.v.) antimicrobial therapy]. CVVHDF parameters were recorded and a PK analysis was performed using serum, urine, and bronchoalveolar lavage fluid samples.
Maximum serum amikacin concentration [median 1.93 (range: 0.63-3.99) mg/L] and area under the concentration-time curve from zero to 12 h on day 3 [median 19.32 (range 6.32-36.87) mg · h/L] were elevated compared with mechanically ventilated patients with normal renal function; however, serum amikacin trough concentrations were within accepted safety limits. The median amikacin concentration in epithelial lining fluid [887 (range: 406-12,819) mg/L] was similar to that reported previously in mechanically ventilated patients with normal renal function. BAY41-6551 demonstrated acceptable safety and tolerability with most adverse events (AEs) as expected for the patient population. One serious AE of bronchospasm was attributed to the study medication; no reported AEs were related to the PDDS Clinical device.
CVVHDF appears to provide adequate clearance of systemically absorbed amikacin in mechanically ventilated patients with ARF, suggesting that dose adjustments for BAY41-6551 are probably not necessary for this patient population. Nonetheless, the standard precautionary measures for critically ill patients receiving i.v. amikacin should be followed for patients with ARF who are treated with BAY41-6551.
BAY41-6551 是一种正在开发的药物-器械联合用药，用于辅助治疗气管插管和机械通气患者的革兰氏阴性肺炎，由吸入用阿米卡星制剂与肺部药物输送系统（PDDS）临床气溶胶输送平台组成。鉴于氨基糖苷类药物主要通过肾脏清除，了解急性肾衰（ARF）患者接受 BAY41-6551 治疗时全身阿米卡星暴露和安全性情况在临床上非常重要。
7 例患有革兰氏阴性肺炎和 ARF 的机械通气患者接受连续静脉-静脉血液透析滤过（CVVHDF）治疗，同时接受 PDDS 临床呼吸机装置多次给药，每日两次，每次 400mg 阿米卡星[此外还接受标准静脉（i.v.）抗菌治疗]。记录 CVVHDF 参数，并使用血清、尿液和支气管肺泡灌洗液样本进行 PK 分析。
第 3 天，最大血清阿米卡星浓度[中位数 1.93（范围：0.63-3.99）mg/L]和 0 至 12 小时的浓度-时间曲线下面积[中位数 19.32（范围：6.32-36.87）mg·h/L]与肾功能正常的机械通气患者相比升高；然而，血清阿米卡星谷浓度在可接受的安全范围内。上皮衬里液中的阿米卡星浓度中位数[887（范围：406-12819）mg/L]与肾功能正常的机械通气患者之前报道的相似。BAY41-6551 表现出良好的安全性和耐受性，大多数不良事件（AE）与患者人群预期一致。1 例严重的 AE 为支气管痉挛，归因于研究药物；无报告的 AE 与 PDDS 临床装置有关。
CVVHDF 似乎为 ARF 机械通气患者提供了足够的全身性吸收阿米卡星清除率，表明该患者人群可能不需要调整 BAY41-6551 的剂量。尽管如此，对于接受静脉内阿米卡星治疗的 ARF 患者，仍应遵循接受静脉内阿米卡星治疗的危重症患者的标准预防措施。
