Burns, Trauma & Critical Care Research Centre, The University of Queensland, Level 7, Block 6, Royal Brisbane and Women's Hospital, Brisbane, QLD 4029, Australia.
Department of Intensive Care Medicine, Level 3, Ned Hanlon Building, Royal Brisbane and Women's Hospital, Brisbane, QLD 4029, Australia.
Int J Antimicrob Agents. 2014 Apr;43(4):343-8. doi: 10.1016/j.ijantimicag.2014.01.009. Epub 2014 Feb 10.
This prospective pharmacokinetic study aimed to describe plasma and interstitial fluid (ISF) pharmacokinetics of piperacillin and tazobactam in critically ill patients on continuous venovenous haemodiafiltration (CVVHDF). Piperacillin/tazobactam (4g/0.5g) was administered every 8h and CVVHDF was performed as a 3-3.5L/h exchange using a polyacrylonitrile filter with a surface area of 1.05m(2). Serial blood (pre- and post-filter), filtrate/dialysate, urine and ISF concentrations were measured. Subcutaneous tissue ISF concentrations were determined using microdialysis. A total of 407 samples were collected. Median peak plasma concentrations were 210.5 (interquartile range=161.5-229.0) and 29.4 (27.9-32.0) mg/L and median trough plasma concentrations were 64.3 (49.0-68.9) and 12.3 (7.7-13.7) mg/L for piperacillin and tazobactam, respectively. The plasma elimination half-life was 6.4 (4.6-8.7) and 7.3 (4.6-11.8) h, volume of distribution 0.42 (0.29-0.49) and 0.32 (0.24-0.36) L/kg, total clearance 5.1 (4.2-6.2) and 3.8 (3.3-4.2) L/h and CVVHDF clearance 2.5 (2.3-3.1) and 2.5 (2.3-3.2) L/h for piperacillin and tazobactam, respectively. The tissue penetration ratio or ratio of area under the concentration-time curve of the unbound drug in ISF to plasma (unbound AUCISF/AUCplasma) was ca. 1 for both piperacillin and tazobactam. This is the first report of concurrent plasma and ISF concentrations of piperacillin and tazobactam during CVVHDF. For the CVVHDF settings used in this study, a dose of 4.5g piperacillin/tazobactam administered evry 8h resulted in piperacillin concentrations in plasma and ISF >32mg/L throughout most of the dosing interval.
这项前瞻性药代动力学研究旨在描述连续静脉-静脉血液透析滤过（CVVHDF）中重症患者哌拉西林和他唑巴坦的血浆和间质液（ISF）药代动力学。哌拉西林/他唑巴坦（4g/0.5g）每 8 小时给药一次，并使用表面积为 1.05m² 的丙烯腈过滤器以 3-3.5L/h 的速度进行 CVVHDF。连续采集血液（滤器前和滤器后）、滤液/透析液、尿液和 ISF 浓度。使用微透析法测定皮下组织 ISF 浓度。共采集 407 个样本。哌拉西林和他唑巴坦的中位峰值血浆浓度分别为 210.5（四分位距=161.5-229.0）和 29.4（27.9-32.0）mg/L，中位谷值血浆浓度分别为 64.3（49.0-68.9）和 12.3（7.7-13.7）mg/L。哌拉西林和他唑巴坦的血浆消除半衰期分别为 6.4（4.6-8.7）和 7.3（4.6-11.8）h，分布容积分别为 0.42（0.29-0.49）和 0.32（0.24-0.36）L/kg，总清除率分别为 5.1（4.2-6.2）和 3.8（3.3-4.2）L/h，CVVHDF 清除率分别为 2.5（2.3-3.1）和 2.5（2.3-3.2）L/h。哌拉西林和他唑巴坦的游离药物在 ISF 中的浓度-时间曲线下面积与血浆（游离 AUCISF/AUCplasma）之比（组织穿透比）约为 1。这是首次报道 CVVHDF 期间同时存在哌拉西林和他唑巴坦的血浆和 ISF 浓度。对于本研究中使用的 CVVHDF 设置，每 8 小时给予 4.5g 哌拉西林/他唑巴坦可使哌拉西林的血浆和 ISF 浓度>32mg/L，在大部分给药间隔内。
