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

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.

• Authors: Danny Tsai, Penelope Stewart, Rajendra Goud, Stephen Gourley, Saliya Hewagama, Sushena Krishnaswamy, Steven C Wallis, Jeffrey Lipman, Jason A Roberts
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 60 Issue 12 Pg. 7402-7406 (12 2016) ISSN: 1098-6596 [Electronic] United States
• PMID: 27736759 (Publication Type: Journal Article)
• Copyright: © Crown copyright 2016.

Chemical References

• Anti-Bacterial Agents
• Creatinine
• Piperacillin

Topics

• APACHE
• Adult
• Anti-Bacterial Agents (blood, pharmacokinetics)
• Body Weight
• Creatinine (blood)
• Critical Illness
• Female
• Humans
• Intensive Care Units
• Male
• Microbial Sensitivity Tests
• Middle Aged
• Native Hawaiian or Other Pacific Islander
• Piperacillin (blood, pharmacokinetics)
• Sepsis (drug therapy, ethnology, microbiology, pathology)