Population pharmacokinetics of the piperacillin component of piperacillin/tazobactam in pediatric oncology patients with fever and neutropenia

Abstract

In children with fever and neutropenia, piperacillin/tazobactam dosing regimens that are administered every 4 hr or that employ prolonged or continuous infusions should be considered to optimize pharmacodynamic exposure.

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

“…Female patients exhibited significantly slower tazobactam CL than male patients, a finding that has not been previously reported. The glomerular filtration rate (GFR), estimated using the modified Schwartz equation (29), was not associated with piperacillin or tazobactam CL, similar to the findings of previous studies (14,15). Potential explanations for this finding include the relatively small sample size (n ϭ 12), the exclusion of patients with an eGFR of Ͻ60 ml/min/1.73 m 2 , or an inaccurate estimate of the patient's actual GFR.…”

“…Previous studies have utilized one-and two-compartment models to describe piperacillin and/or tazobactam serum concentrationtime data in pediatric patients receiving TZP by the traditional 0.5-h infusion (14,15,24,27,28,40). However, the rate constants for the transfer of piperacillin between the central and peripheral compartments are rapid in young children and distribution may be complete (or nearly complete) by the end of the 4-h infusion, which results in a better fit with a one-compartment model (14).…”

“…Pharmacodynamic predictors of efficacy (e.g., T MIC ) for antibiotics do not change from the adult to the child. While evaluations of TZP pharmacokinetics in children are available, there are currently no published pharmacokinetic and pharmacodynamic data from children receiving extended-infusion TZP to guide optimal dosing on the basis of attainment of the target T MIC (14,15,(20)(21)(22)(23)(24)(25)(26)(27)(28). In addition, data regarding the population pharmacokinetics of tazobactam in children are limited (27,28).…”

“…Extended-infusion TZP dosing (with a piperacillin component of 100 mg/kg of body weight given every 8 h and infused over 4 h) was demonstrated to be feasible in over 90% of children, but currently available pediatric data on the pharmacodynamics of extended-infusion TZP are limited to those from Monte Carlo simulations incorporating pharmacokinetic data derived from the single or first dose of TZP infused over 0.5 h (13)(14)(15)(16). Children exhibit pharmacokinetic changes throughout development, and the pharmacokinetics of drugs in children show significant differences from those in adults.…”

Dose optimization of piperacillin/tazobactam in critically ill children

“…[8][9][10] To date, the pharmacokinetics of piperacillin/tazobactam have been described in (pre)term neonates and non-ICU children, but only in a small number of children admitted to the paediatric ICU (n=13 and n=12 patients), between 1 and 9 years of age. 7,[11][12][13][14][15] Any effort to define the dose rationale in infants and young children needs to account for the effect of developmental processes, which are known to affect drug exposure and potentially treatment response. 16 Moreover, the impact of pathophysiological changes on pharmacokinetics has been widely demonstrated in critically ill adults.…”