Biomaterial Database

Population Pharmacokinetics of Piperacillin in Nonobese, Obese, and Morbidly Obese Critically Ill Patients. 2017

Abdulaziz S Alobaid, and Steven C Wallis, and Paul Jarrett, and Therese Starr, and Janine Stuart, and Melissa Lassig-Smith, and Jenny Lisette Ordóñez Mejia, and Michael S Roberts, and Claire Roger, and Andrew A Udy, and Jeffrey Lipman, and Jason A Roberts

Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia.

The treatment of infections in critically ill obese and morbidly obese patients is challenging because of the combined physiological changes that result from obesity and critical illness. The aim of this study was to describe the population pharmacokinetics of piperacillin in a cohort of critically ill patients, including obese and morbidly obese patients. Critically ill patients who received piperacillin-tazobactam were classified according to their body mass index (BMI) as nonobese, obese, and morbidly obese. Plasma samples were collected, and piperacillin concentrations were determined by a validated chromatographic method. Population pharmacokinetic analysis and Monte Carlo dosing simulations were performed using Pmetrics software. Thirty-seven critically ill patients (including 12 obese patients and 12 morbidly obese patients) were enrolled. The patients' mean ± standard deviation age, weight, and BMI were 50 ± 15 years, 104 ± 35 kg, and 38.0 ± 15.0 kg/m2, respectively. The concentration-time data were best described by a two-compartment linear model. The mean ± SD parameter estimates for the final covariate model were a clearance of 14.0 ± 7.1 liters/h, a volume of distribution of the central compartment of 49.0 ± 19.0 liters, an intercompartmental clearance from the central compartment to the peripheral compartment of 0.9 ± 0.6 liters · h-1, and an intercompartmental clearance from the peripheral compartment to the central compartment of 2.3 ± 2.8 liters · h-1 A higher measured creatinine clearance and shorter-duration infusions were associated with a lower likelihood of achieving therapeutic piperacillin exposures in patients in all BMI categories. Piperacillin pharmacokinetics are altered in the presence of obesity and critical illness. As with nonobese patients, prolonged infusions increase the likelihood of achieving therapeutic concentrations.

UI	MeSH Term	Description	Entries
D007262	Infusions, Intravenous	The long-term (minutes to hours) administration of a fluid into the vein through venipuncture, either by letting the fluid flow by gravity or by pumping it.	Drip Infusions,Intravenous Drip,Intravenous Infusions,Drip Infusion,Drip, Intravenous,Infusion, Drip,Infusion, Intravenous,Infusions, Drip,Intravenous Infusion
D008297	Male		Males
D008826	Microbial Sensitivity Tests	Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses).	Bacterial Sensitivity Tests,Drug Sensitivity Assay, Microbial,Minimum Inhibitory Concentration,Antibacterial Susceptibility Breakpoint Determination,Antibiogram,Antimicrobial Susceptibility Breakpoint Determination,Bacterial Sensitivity Test,Breakpoint Determination, Antibacterial Susceptibility,Breakpoint Determination, Antimicrobial Susceptibility,Fungal Drug Sensitivity Tests,Fungus Drug Sensitivity Tests,Sensitivity Test, Bacterial,Sensitivity Tests, Bacterial,Test, Bacterial Sensitivity,Tests, Bacterial Sensitivity,Viral Drug Sensitivity Tests,Virus Drug Sensitivity Tests,Antibiograms,Concentration, Minimum Inhibitory,Concentrations, Minimum Inhibitory,Inhibitory Concentration, Minimum,Inhibitory Concentrations, Minimum,Microbial Sensitivity Test,Minimum Inhibitory Concentrations,Sensitivity Test, Microbial,Sensitivity Tests, Microbial,Test, Microbial Sensitivity,Tests, Microbial Sensitivity
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D009010	Monte Carlo Method	In statistics, a technique for numerically approximating the solution of a mathematical problem by studying the distribution of some random variable, often generated by a computer. The name alludes to the randomness characteristic of the games of chance played at the gambling casinos in Monte Carlo. (From Random House Unabridged Dictionary, 2d ed, 1993)	Method, Monte Carlo
D009767	Obesity, Morbid	The condition of weighing two, three, or more times the ideal weight, so called because it is associated with many serious and life-threatening disorders. In the BODY MASS INDEX, morbid obesity is defined as having a BMI greater than 40.0 kg/m2.	Morbid Obesity,Obesity, Severe,Morbid Obesities,Obesities, Morbid,Obesities, Severe,Severe Obesities,Severe Obesity
D010397	Penicillanic Acid	A building block of penicillin, devoid of significant antibacterial activity. (From Merck Index, 11th ed)	Acid, Penicillanic
D010878	Piperacillin	Semisynthetic, broad-spectrum, AMPICILLIN derived ureidopenicillin antibiotic proposed for PSEUDOMONAS infections. It is also used in combination with other antibiotics.	AB-Piperacillin,Cl-227193,Pipcil,Pipera-Hameln,Piperacillin Curasan,Piperacillin Fresenius,Piperacillin Hexal,Piperacillin Monosodium Salt,Piperacillin Sodium,Piperacillin-Ratiopharm,Pipercillin,Pipracil,Pipril,T-1220,T1220,AB Piperacillin,Cl 227193,Cl227193,Curasan, Piperacillin,Monosodium Salt, Piperacillin,Pipera Hameln,Piperacillin Ratiopharm,Salt, Piperacillin Monosodium,Sodium, Piperacillin,T 1220
D003404	Creatinine		Creatinine Sulfate Salt,Krebiozen,Salt, Creatinine Sulfate,Sulfate Salt, Creatinine
D004334	Drug Administration Schedule	Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience.	Administration Schedule, Drug,Administration Schedules, Drug,Drug Administration Schedules,Schedule, Drug Administration,Schedules, Drug Administration