Therapeutic Drug Monitoring of Amikacin in Neutropenic Oncology Patients

Abstract

Amikacin is the antibiotic of choice for the treatment of Gram-negative infections, namely, those in neutropenic oncology patients. No populational pharmacokinetic studies are currently available reporting amikacin pharmacokinetics in neutropenic oncology patients despite their specific pathophysiological features and treatments. A large-scale retrospective study was herein conducted to specifically investigate the effects that tumor diseases have on the pharmacokinetic parameters of amikacin and identify whether chemotherapy, the lag time between administration of chemotherapy and amikacin, age and renal function contribute to amikacin pharmacokinetics in neutropenic cancer patients. A total of 1180 pharmacokinetic analysis from 629 neutropenic patients were enrolled. The daily dose administered to oncology patients was higher than that administered to non-oncology patients (p < 0.0001). No statistical differences were found in amikacin concentrations, probably because drug clearance was increased in cancer patients (p < 0.0001). Chemotherapy influenced amikacin pharmacokinetics and drug clearance decreased as the lag time enhanced. The elderly group revealed no statistical differences between the doses administered to both the oncology groups, suggesting that the impact of ageing is stronger than chemotherapy. Our research suggests that cancer patients require higher initial doses of amikacin, as well as when chemotherapy is received less than 30 days before amikacin treatment has started.

Keywords: amikacin; antibiotics; neutropenia; pharmacokinetics; therapeutic drug monitoring; tumor.

Figure 1

Pharmacokinetic (PK) analysis performed on each group herein investigated. Control Group includes neutropenic non-oncology patients, while Test Group includes neutropenic oncology patients that were distinguished in accordance with the last administered chemotherapy cycle: “with chemotherapy” includes those that received chemotherapy cycle; “without chemotherapy” includes patients that received other therapy but not chemotherapy. Each pharmacokinetic monitoring required the determination of the peak and trough concentrations and the estimation of the corresponding pharmacokinetic parameters.