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

BMC Clinical Pharmacology

Jorge A Cortés³  Ricardo Sánchez¹  Edelberto Silva²  Jorge Augusto Díaz⁵  Julio C Gómez⁴  Javier R Garzón¹  Sonia I Cuervo⁴  José C Álvarez³ 

[1](GREICAH): Grupo de Investigación en Enfermedades Infecciosas en Cáncer y alteraciones hematológicas, Bogotá, Colombia

[2]Departamento de Medicina, Facultad de Medicina, Ciudad Universitaria, Carrera 30 No. 45-03, edificio 471, oficina 510, Bogotá, A. A. 14490, Colombia

[3]Universidad Nacional de Colombia, Facultad de Medicina, Bogotá, Colombia

[4]Instituto Nacional de Cancerología, Bogotá, Colombia

[5]Departamento de Farmacia, Facultad de Ciencias, Universidad Nacional de Colombia, Bogotá, Colombia

关键词: Hematological malignancies;    Chemotherapy;    Fever;    Neutropenia;    Beta-lactam antibiotics;    Piperacillin/tazobactam;    Pharmacokinetics;   

Others  :  860482
DOI  :  10.1186/2050-6511-14-59

 received in 2012-11-29, accepted in 2013-11-15,  发布年份 2013

【 摘 要 】

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.

Methods

This 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.

Results

We 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 (t_1/2), 0.55–2.65 h (mean, 1.38 h); and area under the curve, 115.12–827.16 mg · h/L.

Conclusion

Patients 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 t_1/2 and decreased CL.

【 授权许可】

   
2013 Álvarez et al.; licensee BioMed Central Ltd.

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