Pharmacokinetics of piperacillin/tazobactam in cancer patients with hematological malignancies and febrile neutropenia after chemotherapy

José C Álvarez,Jorge A Cortés,Julio C Gómez,Ricardo Sánchez,Edelberto Silva,Jorge Augusto Díaz,Sonia I Cuervo,Javier R Garzón

doi:10.1186/2050-6511-14-59

Abstract

IntroductionPatients with febrile neutropenia (FN) exhibit changes in extracellular fluid that may alter the plasma concentrations of beta-lactams and result in therapeutic failure or toxicity. We evaluated the pharmacokinetics of piperacillin/tazobactam in patients with hematological malignancies and FN after receiving chemotherapy at a primary public cancer center.MethodsThis was an open, nonrandomized, observational, descriptive, and prospective study. Samples from 15 patients with hematological malignancies and FN were evaluated after the administration of chemotherapy. Five blood samples were taken from each patient when the antibiotic level was at steady-state 10, 60, 120, 180, and 350 min after each dose. Antibiotic concentrations were measured using gel diffusion with Bacillus subtilis. All study participants provided written informed consent.ResultsWe investigated the pharmacokinetics of piperacillin in 14 patients between the ages of 18 years and 59 years and with a mean absolute neutrophil count of 208 cells per mm3 (standard deviation (SD) ± 603.2). The following pharmacokinetic measurements were obtained: maximum concentration, 94.1–1133 mg/L; minimum concentration, 0.47–37.65 mg/L; volume of distribution, 0.08–0.65 L/kg (mean, 0.34 L/kg); drug clearance (CL), 4.42–27.25 L/h (mean, 9.93 L/h); half-life (t1/2), 0.55–2.65 h (mean, 1.38 h); and area under the curve, 115.12–827.16 mg · h/L.ConclusionPatients with FN after receiving chemotherapy exhibited significant variations in the pharmacokinetic parameters of piperacillin compared with healthy individuals; specifically, FN patients demonstrated an increase in t1/2 and decreased CL.

Highlights

Patients with febrile neutropenia (FN) exhibit changes in extracellular fluid that may alter the plasma concentrations of beta-lactams and result in therapeutic failure or toxicity
Addition of piperacillin or amikacin to moxalactam administration in FN patients has been shown to alter PK parameters compared with healthy individuals [4], and a randomized clinical trial evaluating PK parameters demonstrated a decrease in the volume of distribution (Vd) and drug clearance (CL) and an increase in half-life (t1⁄2) [5]
PK parameters were compared between group of patients with albumin levels >3 g/dLvs. those with

Summary

Introduction

Patients with febrile neutropenia (FN) exhibit changes in extracellular fluid that may alter the plasma concentrations of beta-lactams and result in therapeutic failure or toxicity. We evaluated the pharmacokinetics of piperacillin/tazobactam in patients with hematological malignancies and FN after receiving chemotherapy at a primary public cancer center. Beta-lactams are the first-choice antibiotics for the treatment of FN after chemotherapy, and inadequate serum levels of these antibiotics may lead to therapeutic failure. Piperacillin/tazobactam, imipenem/cilastatin, and meropenem are beta-lactam antibiotics that exhibit activity against Pseudomonas aeruginosa, and these antibiotics are recommended as monotherapy for the empirical treatment of FN after chemotherapy [3]. We investigated the PK parameters of piperacillin in Latin American patients with hematological malignancies and FN after receiving chemotherapy Addition of piperacillin or amikacin to moxalactam administration in FN patients has been shown to alter PK parameters compared with healthy individuals [4], and a randomized clinical trial evaluating PK parameters demonstrated a decrease in the volume of distribution (Vd) and drug clearance (CL) and an increase in half-life (t1⁄2) [5].

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