TY - JOUR
T1 - Pharmacokinetics of piperacillin in critically ill Australian Indigenous patients with severe sepsis
AU - Tsai, Danny
AU - Stewart, Penelope
AU - Goud, Rajendra
AU - Gourley, Stephen
AU - Hewagama, Saliya
AU - Krishnaswamy, Sushena
AU - Wallis, Steven C.
AU - Lipman, Jeffrey
AU - Roberts, Jason A.
PY - 2016/12
Y1 - 2016/12
N2 - 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.
AB - 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.
KW - Piperacillin
KW - Sepsis
KW - Indigenous Australia
KW - pharmacokinetic study
UR - http://www.scopus.com/inward/record.url?scp=84996536332&partnerID=8YFLogxK
UR - http://purl.org/au-research/grants/NHMRC/1074523
UR - http://purl.org/au-research/grants/NHMRC/1099452
UR - http://purl.org/au-research/grants/NHMRC/1048652
U2 - 10.1128/AAC.01657-16
DO - 10.1128/AAC.01657-16
M3 - Article
C2 - 27736759
AN - SCOPUS:84996536332
SN - 0066-4804
VL - 60
SP - 7402
EP - 7406
JO - Antimicrobial agents and chemotherapy
JF - Antimicrobial agents and chemotherapy
IS - 12
ER -