Buckwalter Mary, Dowell James A
Vicuron Pharmaceuticals, King of Prussia, PA 19406, USA.
J Clin Pharmacol. 2005 Nov;45(11):1279-87. doi: 10.1177/0091270005280378.
Dalbavancin is a lipoglycopeptide antibiotic in clinical development as a once-weekly treatment for serious infections. A total of 532 patients, consisting of 502 patients with skin and soft tissue infections requiring parenteral therapy and 30 patients with catheter-related bloodstream infections, was available for population pharmacokinetic analysis. The majority of patients (78.4%) received dalbavancin intravenously as a 1000-mg dose on day 1 and a single 500-mg dose on day 8. A 2-compartment model with first-order elimination provided the best fit to the data. The clearance of dalbavancin was influenced by body surface area and creatinine clearance, but together they described less than 25% of the interpatient variability. Body surface area was determined to be a predictor of the central volume of distribution. There was no evidence that the presence of metabolic substrates, inhibitors, or inducers of cytochrome P450 or selected concomitant medications influenced the clearance of dalbavancin.
达巴万星是一种脂糖肽类抗生素，正处于临床开发阶段，用于严重感染的每周一次治疗。共有532例患者可用于群体药代动力学分析，其中包括502例需要肠外治疗的皮肤和软组织感染患者以及30例导管相关血流感染患者。大多数患者（78.4%）在第1天接受1000mg剂量静脉注射达巴万星，在第8天接受单次500mg剂量。具有一级消除的二室模型最符合数据。达巴万星的清除率受体表面积和肌酐清除率影响，但两者共同描述的患者间变异性不到25%。体表面积被确定为中央分布容积的预测因子。没有证据表明细胞色素P450的代谢底物、抑制剂或诱导剂的存在或选定的伴随用药会影响达巴万星的清除率。
