Conor J. O'Hanlon, Nick Holford, Brian J. Anderson, Mark Greaves, Lee Blackburn, Malcolm D. Tingle, Jacqueline A. Hannam
{"title":"描述抗生素在心肺旁路装置上吸附的药代动力学框架。","authors":"Conor J. O'Hanlon, Nick Holford, Brian J. Anderson, Mark Greaves, Lee Blackburn, Malcolm D. Tingle, Jacqueline A. Hannam","doi":"10.1002/psp4.13180","DOIUrl":null,"url":null,"abstract":"<p>Cardiopulmonary bypass (CPB) can alter pharmacokinetic (PK) parameters and the drug may adsorb to the CPB device, altering exposure. Cefazolin is a beta-lactam antibiotic used for antimicrobial prophylaxis during cardiac surgery supported by CPB. Adsorption of cefazolin could result in therapeutic failure. An ex vivo study was undertaken using CPB devices primed and then dosed with cefazolin and samples were obtained over 1 hour of recirculation. Twelve experimental runs were conducted using different CPB device sizes (neonate, infant, child, and adult), device coatings (Xcoating™, Rheoparin®, PH.I.S.I.O), and priming solutions. The time course of saturable binding, using <i>B</i><sub>max</sub> (binding capacity), <i>K</i><sub>d</sub> (dissociation constant), and T2<sub>off</sub> (half-time of dissociation), described cefazolin adsorption. <i>B</i><sub>max</sub> estimates for the device sizes were neonate 40.0 mg (95% CI 24.3, 67.4), infant 48.6 mg (95% CI 5.97, 80.2), child 77.8 mg (95% CI 54.9, 103), and adult 196 mg (95% CI 191, 199). The Xcoating™ <i>K</i><sub>d</sub> estimate was 139 mg/L (95% CI 27.0, 283) and the T2<sub>off</sub> estimate was 98.4 min (95% CI 66.8, 129). The Rheoparin® and PH.I.S.I.O coatings had similar binding parameters with <i>K</i><sub>d</sub> and T2<sub>off</sub> estimates of 0.169 mg/L (95% CI 0.01, 1.99) and 4.94 min (95% CI 0.17, 59.4). The <i>B</i><sub>max</sub> was small (< 10%) relative to a typical total patient dose during cardiac surgery supported by CPB. A dose adjustment for cefazolin based solely on drug adsorption is not required. This framework could be extended to other PK studies involving CPB.</p>","PeriodicalId":10774,"journal":{"name":"CPT: Pharmacometrics & Systems Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.1000,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/psp4.13180","citationCount":"0","resultStr":"{\"title\":\"A pharmacokinetic framework describing antibiotic adsorption to cardiopulmonary bypass devices\",\"authors\":\"Conor J. O'Hanlon, Nick Holford, Brian J. Anderson, Mark Greaves, Lee Blackburn, Malcolm D. Tingle, Jacqueline A. Hannam\",\"doi\":\"10.1002/psp4.13180\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Cardiopulmonary bypass (CPB) can alter pharmacokinetic (PK) parameters and the drug may adsorb to the CPB device, altering exposure. Cefazolin is a beta-lactam antibiotic used for antimicrobial prophylaxis during cardiac surgery supported by CPB. Adsorption of cefazolin could result in therapeutic failure. An ex vivo study was undertaken using CPB devices primed and then dosed with cefazolin and samples were obtained over 1 hour of recirculation. Twelve experimental runs were conducted using different CPB device sizes (neonate, infant, child, and adult), device coatings (Xcoating™, Rheoparin®, PH.I.S.I.O), and priming solutions. The time course of saturable binding, using <i>B</i><sub>max</sub> (binding capacity), <i>K</i><sub>d</sub> (dissociation constant), and T2<sub>off</sub> (half-time of dissociation), described cefazolin adsorption. <i>B</i><sub>max</sub> estimates for the device sizes were neonate 40.0 mg (95% CI 24.3, 67.4), infant 48.6 mg (95% CI 5.97, 80.2), child 77.8 mg (95% CI 54.9, 103), and adult 196 mg (95% CI 191, 199). The Xcoating™ <i>K</i><sub>d</sub> estimate was 139 mg/L (95% CI 27.0, 283) and the T2<sub>off</sub> estimate was 98.4 min (95% CI 66.8, 129). The Rheoparin® and PH.I.S.I.O coatings had similar binding parameters with <i>K</i><sub>d</sub> and T2<sub>off</sub> estimates of 0.169 mg/L (95% CI 0.01, 1.99) and 4.94 min (95% CI 0.17, 59.4). The <i>B</i><sub>max</sub> was small (< 10%) relative to a typical total patient dose during cardiac surgery supported by CPB. A dose adjustment for cefazolin based solely on drug adsorption is not required. 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引用次数: 0
摘要
心肺旁路术(CPB)会改变药代动力学(PK)参数,药物可能会吸附在 CPB 设备上,从而改变暴露量。头孢唑啉是一种β-内酰胺类抗生素,用于 CPB 支持下的心脏手术的抗菌预防。头孢唑啉的吸附可能导致治疗失败。我们使用 CPB 设备进行了一项体内外研究,先用头孢唑啉进行预处理,然后在再循环的 1 小时内采集样本。使用不同的 CPB 装置尺寸(新生儿、婴儿、儿童和成人)、装置涂层(Xcoating™、Rheoparin®、PH.I.S.I.O)和引导溶液进行了 12 次实验。利用 Bmax(结合能力)、Kd(解离常数)和 T2off(解离半衰期)描述了头孢唑啉吸附的饱和结合时间过程。装置尺寸的 Bmax 估计值分别为新生儿 40.0 毫克(95% CI 24.3,67.4)、婴儿 48.6 毫克(95% CI 5.97,80.2)、儿童 77.8 毫克(95% CI 54.9,103)和成人 196 毫克(95% CI 191,199)。Xcoating™ Kd估计值为139毫克/升(95% CI 27.0,283),T2off估计值为98.4分钟(95% CI 66.8,129)。Rheoparin®和PH.I.S.I.O涂层的结合参数相似,Kd和T2off估计值分别为0.169毫克/升(95% CI 0.01,1.99)和4.94分钟(95% CI 0.17,59.4)。Bmax 较小 (
A pharmacokinetic framework describing antibiotic adsorption to cardiopulmonary bypass devices
Cardiopulmonary bypass (CPB) can alter pharmacokinetic (PK) parameters and the drug may adsorb to the CPB device, altering exposure. Cefazolin is a beta-lactam antibiotic used for antimicrobial prophylaxis during cardiac surgery supported by CPB. Adsorption of cefazolin could result in therapeutic failure. An ex vivo study was undertaken using CPB devices primed and then dosed with cefazolin and samples were obtained over 1 hour of recirculation. Twelve experimental runs were conducted using different CPB device sizes (neonate, infant, child, and adult), device coatings (Xcoating™, Rheoparin®, PH.I.S.I.O), and priming solutions. The time course of saturable binding, using Bmax (binding capacity), Kd (dissociation constant), and T2off (half-time of dissociation), described cefazolin adsorption. Bmax estimates for the device sizes were neonate 40.0 mg (95% CI 24.3, 67.4), infant 48.6 mg (95% CI 5.97, 80.2), child 77.8 mg (95% CI 54.9, 103), and adult 196 mg (95% CI 191, 199). The Xcoating™ Kd estimate was 139 mg/L (95% CI 27.0, 283) and the T2off estimate was 98.4 min (95% CI 66.8, 129). The Rheoparin® and PH.I.S.I.O coatings had similar binding parameters with Kd and T2off estimates of 0.169 mg/L (95% CI 0.01, 1.99) and 4.94 min (95% CI 0.17, 59.4). The Bmax was small (< 10%) relative to a typical total patient dose during cardiac surgery supported by CPB. A dose adjustment for cefazolin based solely on drug adsorption is not required. This framework could be extended to other PK studies involving CPB.