Pharmacokinetics of piperacillin in critically ill Australian Indigenous patients with severe sepsis

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

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)7402-7406
Number of pages5
JournalAntimicrobial agents and chemotherapy
Volume60
Issue number12
DOIs
Publication statusPublished - Dec 2016
Externally publishedYes

Keywords

  • Piperacillin
  • Sepsis
  • Indigenous Australia
  • pharmacokinetic study

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