title: Pharmacokinetics of piperacillin/tazobactam in cancer patients with hematological malignancies and febrile neutropenia after chemotherapy.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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 t1(/2) and decreased CL.
authors.affiliation: (GREICAH): Grupo de Investigación en Enfermedades Infecciosas en Cáncer y alteraciones hematológicas, Bogotá, Colombia. esilvag@unal.edu.co.
authors.forename: José C
authors.initials: JC
authors.lastname: Álvarez
authors.forename: Sonia I
authors.initials: SI
authors.lastname: Cuervo
authors.forename: Javier R
authors.initials: JR
authors.lastname: Garzón
authors.forename: Julio C
authors.initials: JC
authors.lastname: Gómez
authors.forename: Jorge Augusto
authors.initials: JA
authors.lastname: Díaz
authors.forename: Edelberto
authors.initials: E
authors.lastname: Silva
authors.forename: Ricardo
authors.initials: R
authors.lastname: Sánchez
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Cortés
mesh_terms: D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D064146:Chemotherapy-Induced Febrile Neutropenia / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D005260:Female; D019337:Hematologic Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000166:cytology; D010397:Penicillanic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D010878:Piperacillin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D000077725:Piperacillin, Tazobactam Drug Combination; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D000077725:Piperacillin, Tazobactam Drug Combination; D010397:Penicillanic Acid; D010878:Piperacillin