Population Pharmacokinetics and Pharmacodynamics of Extended-Infusion Piperacillin and Tazobactam in Critically Ill Children

Authors

Chad A. Knoderer, Butler UniversityFollow
Kristen R. Nichols, Butler UniversityFollow
Eun Kyoung Chung
Lauren E. Buenger
Daniel P. Healy
Jennifer Dees
Ashley S. Crumby
Michael B. Kays

Document Type

Article

Publication Date

2016

Publication Title

Antimicrobial Agents and Chemotherapy

First Page

522

Last Page

531

DOI

http://dx.doi.org/10.1128/AAC.02089-15

Abstract

The study objective was to evaluate the population pharmacokinetics and pharmacodynamics of extended-infusion piperacillintazobactam in children hospitalized in an intensive care unit. Seventy-two serum samples were collected at steady state from 12 patients who received piperacillin-tazobactam at 100/12.5 mg/kg of body weight every 8 h infused over 4 h. Population pharmacokinetic analyses were performed using NONMEM, and Monte Carlo simulations were performed to estimate the piperacillin pharmacokinetic profiles for dosing regimens of 80 to 100 mg/kg of the piperacillin component given every 6 to 8 h and infused over 0.5, 3, or 4 h. The probability of target attainment (PTA) for a cumulative percentage of the dosing interval that the drug concentration exceeds the MIC under steady-state pharmacokinetic conditions (T_MIC) of>50% was calculated at MICs ranging from 0.25 to 64 mg/liter. The mean ± standard deviation (SD) age, weight, and estimated glomerular filtration rate were 5 ± 3 years, 17 ± 6.2 kg, and 118 ± 41 ml/min/1.73m², respectively. A one-compartment model with zero-order input and first-order elimination best fit the pharmacokinetic data for both drugs. Weight was significantly associated with piperacillin clearance, and weight and sex were significantly associated with tazobactam clearance. Pharmacokinetic parameters (mean ± SD) for piperacillin and tazobactam were as follows: clearance, 0.22 ± 0.07 and 0.19 ± 0.07 liter/h/kg, respectively; volume of distribution, 0.43 ± 0.16 and 0.37 ± 0.14 liter/kg, respectively. All extended-infusion regimens achieved PTAs of>90% at MICs of/liter. Only the 3-h infusion regimens given every 6 h achieved PTAs of>90% at an MIC of 32 mg/liter. For susceptible bacterial pathogens, piperacillin-tazobactam doses of>80/10 mg/kg given every 8 h and infused over 4 h achieve adequate pharmacodynamic exposures in critically ill children.

Rights

This article was originally published in Antimicrobial Agents and Chemotherapy,2016, Volume 60, Issue 1.

Recommended Citation

Knoderer, Chad A.; Nichols, Kristen R.; Chung, Eun Kyoung; Buenger, Lauren E.; Healy, Daniel P.; Dees, Jennifer; Crumby, Ashley S.; and Kays, Michael B., "Population Pharmacokinetics and Pharmacodynamics of Extended-Infusion Piperacillin and Tazobactam in Critically Ill Children" (2016). Scholarship and Professional Work – COPHS. 240.
https://digitalcommons.butler.edu/cophs_papers/240