{"title":"哌拉西林/他唑巴坦的药代动力学和治疗监测。","authors":"Veronika Kubíčková, Karel Urbánek","doi":"","DOIUrl":null,"url":null,"abstract":"<p><p>Given their wide therapeutic index, beta-lactam antibiotics are commonly used to treat critically ill patients. It is in these patients that significant heterogeneity in pharmacokinetics was noted, compared to the population average, especially in the volume of distribution, drug clearance and biological half-life, with values increasing as much as two-fold or, in the case of biological half-life, as much as four-fold. Significant pharmacokinetic changes also occur in cases of morbid obesity or renal insufficiency and when complex surgical techniques such as extracorporeal circulation are used. Therapeutic monitoring of piperacillin/tazobactam is a way to personalize and optimize therapy for these groups of patients. Preclinical data show a correlation between the probability of therapeutic success and concentrations of the unbound fraction of an antibiotic exceeding the minimum inhibitory concentration (MIC) for 40-50 % of the dosing interval. This time appears to be the preferred pharmacodynamic target for beta-lactam antibiotics. In critically ill patients, however, an even higher target may be required, ideally 100 % fT > 4xMIC. A better pharmacodynamic profile can be obtained using prolonged or continuous infusion. The biggest obstacle to routine TDM in β-lactams is the speed of quality sample determination. Currently, the most widely used method of measuring plasma concentrations is liquid chromatography coupled with UV or MS detection.</p>","PeriodicalId":17909,"journal":{"name":"Klinicka mikrobiologie a infekcni lekarstvi","volume":"26 3","pages":"86-94"},"PeriodicalIF":0.0000,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"[Pharmacokinetics and therapeutic monitoring of piperacillin/tazobactam].\",\"authors\":\"Veronika Kubíčková, Karel Urbánek\",\"doi\":\"\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Given their wide therapeutic index, beta-lactam antibiotics are commonly used to treat critically ill patients. It is in these patients that significant heterogeneity in pharmacokinetics was noted, compared to the population average, especially in the volume of distribution, drug clearance and biological half-life, with values increasing as much as two-fold or, in the case of biological half-life, as much as four-fold. Significant pharmacokinetic changes also occur in cases of morbid obesity or renal insufficiency and when complex surgical techniques such as extracorporeal circulation are used. Therapeutic monitoring of piperacillin/tazobactam is a way to personalize and optimize therapy for these groups of patients. Preclinical data show a correlation between the probability of therapeutic success and concentrations of the unbound fraction of an antibiotic exceeding the minimum inhibitory concentration (MIC) for 40-50 % of the dosing interval. This time appears to be the preferred pharmacodynamic target for beta-lactam antibiotics. In critically ill patients, however, an even higher target may be required, ideally 100 % fT > 4xMIC. A better pharmacodynamic profile can be obtained using prolonged or continuous infusion. The biggest obstacle to routine TDM in β-lactams is the speed of quality sample determination. Currently, the most widely used method of measuring plasma concentrations is liquid chromatography coupled with UV or MS detection.</p>\",\"PeriodicalId\":17909,\"journal\":{\"name\":\"Klinicka mikrobiologie a infekcni lekarstvi\",\"volume\":\"26 3\",\"pages\":\"86-94\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2020-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Klinicka mikrobiologie a infekcni lekarstvi\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Klinicka mikrobiologie a infekcni lekarstvi","FirstCategoryId":"1085","ListUrlMain":"","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0
摘要
鉴于其广泛的治疗指数,β -内酰胺类抗生素通常用于治疗危重患者。与人群平均水平相比,这些患者在药代动力学方面存在显著的异质性,特别是在分布量、药物清除率和生物半衰期方面,其值增加了两倍,在生物半衰期的情况下,增加了四倍。在病态肥胖或肾功能不全的情况下,以及使用复杂的手术技术(如体外循环)时,也会发生显著的药代动力学变化。哌拉西林/他唑巴坦的治疗监测是个性化和优化治疗的一种方法。临床前数据显示,在40- 50%的给药间隔内,治疗成功的概率与抗生素的未结合部分超过最低抑制浓度(MIC)的浓度之间存在相关性。这段时间似乎是β -内酰胺类抗生素的首选药效学靶点。然而,对于危重患者,可能需要更高的目标,理想情况下是100% fT > 4 * mic。长期或持续输注可获得更好的药效学特征。常规TDM测定β-内酰胺的最大障碍是质量样品的测定速度。目前,最广泛使用的测定血浆浓度的方法是液相色谱联用紫外或质谱检测。
[Pharmacokinetics and therapeutic monitoring of piperacillin/tazobactam].
Given their wide therapeutic index, beta-lactam antibiotics are commonly used to treat critically ill patients. It is in these patients that significant heterogeneity in pharmacokinetics was noted, compared to the population average, especially in the volume of distribution, drug clearance and biological half-life, with values increasing as much as two-fold or, in the case of biological half-life, as much as four-fold. Significant pharmacokinetic changes also occur in cases of morbid obesity or renal insufficiency and when complex surgical techniques such as extracorporeal circulation are used. Therapeutic monitoring of piperacillin/tazobactam is a way to personalize and optimize therapy for these groups of patients. Preclinical data show a correlation between the probability of therapeutic success and concentrations of the unbound fraction of an antibiotic exceeding the minimum inhibitory concentration (MIC) for 40-50 % of the dosing interval. This time appears to be the preferred pharmacodynamic target for beta-lactam antibiotics. In critically ill patients, however, an even higher target may be required, ideally 100 % fT > 4xMIC. A better pharmacodynamic profile can be obtained using prolonged or continuous infusion. The biggest obstacle to routine TDM in β-lactams is the speed of quality sample determination. Currently, the most widely used method of measuring plasma concentrations is liquid chromatography coupled with UV or MS detection.