title: 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 Vcwere found to be described by creatinine clearance (CLCR) and total body weight, respectively. In this patient population, piperacillin demonstrated high interindividual pharmacokinetic variability. CLCRwas found to be the most important determinant of piperacillin pharmacokinetics.
authors.affiliation: Burns, Trauma and Critical Care Research Centre, School of Medicine, The University of Queensland, Brisbane, Queensland, Australia d.tsai@uq.edu.au.|Department of Intensive Care Medicine, Alice Springs Hospital, Alice Springs, Northern Territory, Australia.|Pharmacy Department, Alice Springs Hospital, Alice Springs, Northern Territory, Australia.
authors.forename: Danny
authors.identifier: 0000-0002-7059-8808
authors.initials: D
authors.lastname: Tsai
authors.affiliation: Department of Intensive Care Medicine, Alice Springs Hospital, Alice Springs, Northern Territory, Australia.
authors.forename: Penelope
authors.initials: P
authors.lastname: Stewart
authors.affiliation: Department of Intensive Care Medicine, Alice Springs Hospital, Alice Springs, Northern Territory, Australia.
authors.forename: Rajendra
authors.initials: R
authors.lastname: Goud
authors.affiliation: Emergency Department, Alice Springs Hospital, Alice Springs, Northern Territory, Australia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Gourley
authors.affiliation: Department of Medicine, Alice Springs Hospital, Alice Springs, Northern Territory, Australia.|Department of Infectious Diseases, The Northern Hospital, Epping, Melbourne, Victoria, Australia.
authors.forename: Saliya
authors.initials: S
authors.lastname: Hewagama
authors.affiliation: Department of Medicine, Alice Springs Hospital, Alice Springs, Northern Territory, Australia.|Monash Infectious Diseases, Monash Health, Clayton, Melbourne, Victoria, Australia.
authors.forename: Sushena
authors.initials: S
authors.lastname: Krishnaswamy
authors.affiliation: Burns, Trauma and Critical Care Research Centre, School of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Wallis
authors.affiliation: Burns, Trauma and Critical Care Research Centre, School of Medicine, The University of Queensland, Brisbane, Queensland, Australia.|Department of Intensive Care Medicine, The Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lipman
authors.affiliation: Burns, Trauma and Critical Care Research Centre, School of Medicine, The University of Queensland, Brisbane, Queensland, Australia.|Department of Intensive Care Medicine, The Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.|School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Roberts
mesh_terms: D018806:APACHE; D000328:Adult; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics*; D001835:Body Weight; D003404:Creatinine / Q000097:blood; D016638:Critical Illness; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D010878:Piperacillin / Q000097:blood / Q000493:pharmacokinetics*; D018805:Sepsis / Q000188:drug therapy* / Q000208:ethnology / Q000382:microbiology / Q000473:pathology
chemical_list: D000900:Anti-Bacterial Agents; D003404:Creatinine; D010878:Piperacillin