Pharmacokinetics of Piperacillin in Critically Ill Australian Indigenous Patients with Severe Sepsis.

نویسندگان

  • Danny Tsai
  • Penelope Stewart
  • Rajendra Goud
  • Stephen Gourley
  • Saliya Hewagama
  • Sushena Krishnaswamy
  • Steven C Wallis
  • Jeffrey Lipman
  • Jason A Roberts
چکیده

There are no available pharmacokinetic data to guide piperacillin dosing in critically ill Australian Indigenous patients despite numerous reported physiological differences. This study aimed to describe the population pharmacokinetics of piperacillin in critically ill Australian Indigenous patients with severe sepsis. A population pharmacokinetic study of Indigenous patients with severe sepsis was conducted in a remote hospital intensive care unit. Plasma samples were collected over two dosing intervals and assayed by validated chromatography. Population pharmacokinetic modeling was conducted using Pmetrics. Nine patients were recruited, and a two-compartment model adequately described the data. The piperacillin clearance (CL), volume of distribution of the central compartment (Vc), and distribution rate constants from the central to the peripheral compartment and from the peripheral to the central compartment were 5.6 ± 3.2 liters/h, 14.5 ± 6.6 liters, 1.5 ± 0.4 h-1, and 1.8 ± 0.9 h-1, respectively, where CL and Vc were found to be described by creatinine clearance (CLCR) and total body weight, respectively. In this patient population, piperacillin demonstrated high interindividual pharmacokinetic variability. CLCR was found to be the most important determinant of piperacillin pharmacokinetics.

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عنوان ژورنال:
  • Antimicrobial agents and chemotherapy

دوره 60 12  شماره 

صفحات  -

تاریخ انتشار 2016