Burns, Trauma and Critical Care Research Centre, UQ Centre for Clinical Research, The University of Queensland, Brisbane, Australia; Centre of Translational Pharmacodynamics, School of Pharmacy, The University of Queensland, Brisbane, Australia.
Burns, Trauma and Critical Care Research Centre, UQ Centre for Clinical Research, The University of Queensland, Brisbane, Australia.
J Pharm Biomed Anal. 2018 Jan 30;148:324-333. doi: 10.1016/j.jpba.2017.10.023. Epub 2017 Oct 25.
Piperacillin-tazobactam is a beta-lactam/beta-lactamase combination antibiotic used in patients with moderate to severe infection. Dosing of piperacillin-tazobactam requires an understanding of this patient group to maximise the effectiveness of this antibiotic and limit a further emergence of resistant pathogens. This is the first method that measures piperacillin and tazobactam simultaneously, across this range of clinically-relevant biological matrices. The calibration line was linear across the concentration range of 0.5-500μg/mL for piperacillin and 0.625-62.5μg/mL for tazobactam. All validation testing for matrix effects, precision and accuracy, specificity and stability were within 15%. A calibration equivalence study was performed to investigate the suitability of applying calibration curves prepared in an alternative matrix, with a mean bias of -10.8% identified for the application of a calibration line prepared for tazobactam in plasma only. Bias for all other calibration lines prepared in alternate matrices was within the 5% acceptance criteria. The method was successfully applied to a pharmacokinetic study of a critically ill patient receiving renal replacement therapy, with the results included.
哌拉西林他唑巴坦是一种β-内酰胺/β-内酰胺酶复合抗生素，用于治疗中重度感染的患者。哌拉西林他唑巴坦的剂量需要了解患者群体，以最大限度地提高这种抗生素的有效性，并限制耐药病原体的进一步出现。这是首次在这种临床相关的生物基质范围内同时测量哌拉西林和他唑巴坦的方法。哌拉西林的校准线在 0.5-500μg/mL 的浓度范围内呈线性，他唑巴坦的校准线在 0.625-62.5μg/mL 的浓度范围内呈线性。所有关于基质效应、精密度和准确度、特异性和稳定性的验证测试都在 15%以内。进行了校准等效性研究，以调查在替代基质中应用校准曲线的适用性，结果表明，仅在血浆中制备他唑巴坦校准曲线的应用存在平均偏差-10.8%。在其他替代基质中制备的所有校准线的偏差均在 5%的可接受标准范围内。该方法成功应用于接受肾脏替代治疗的危重症患者的药代动力学研究，并包含了研究结果。
