Population pharmacokinetics of amikacin in patients with haematological malignancies

The aim of this study was to analyse the pharmacokinetic behaviour of amikacin in patients with haematological malignancies using a mixed-effect model and sparse data collected during routine clinical care. The patient population comprised 207 haematology patients divided into two groups: one for co...

Full description

Saved in:
Bibliographic Details
Published in:Journal of antimicrobial chemotherapy 1999-08, Vol.44 (2), p.235-242
Main Authors: ROMANO, S, FDEZ DE GATTA, M. M, CALVO, M. V, CABALLERO, D, DOMINGUEZ-GIL, A, LANAO, J. M
Format: Article
Language:English
Subjects:
Adult
Aged
Amikacin - blood
Amikacin - pharmacokinetics
Amikacin - therapeutic use
Anti-Bacterial Agents - blood
Anti-Bacterial Agents - pharmacokinetics
Anti-Bacterial Agents - therapeutic use
Antibacterial agents
Antibiotics. Antiinfectious agents. Antiparasitic agents
Biological and medical sciences
Female
Hematologic Neoplasms - complications
Hematologic Neoplasms - immunology
Hematologic Neoplasms - metabolism
Humans
Male
Medical sciences
Middle Aged
Models, Biological
Neutropenia - complications
Neutropenia - immunology
Opportunistic Infections - complications
Opportunistic Infections - drug therapy
Pharmacology. Drug treatments
Reproducibility of Results
Retrospective Studies
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The aim of this study was to analyse the pharmacokinetic behaviour of amikacin in patients with haematological malignancies using a mixed-effect model and sparse data collected during routine clinical care. The patient population comprised 207 haematology patients divided into two groups: one for computing the population model (n = 134) and the other for validation (n = 73). A one-compartment model was used and the following covariates were tested for their influence on clearance and volume of distribution: age, gender, weight, parenteral nutrition, creatinine clearance, stage of antineoplastic treatment (induction, consolidation, intensification), number of weeks postchemotherapy, clinical diagnosis, Eastern Cooperative Oncology Group score, neutropenia, hypoalbuminaemia, concomitant medication (vancomycin and/or amphotericin B), overhydration, and autologous or allogenic bone marrow transplant. The nonlinear mixed-effect model (NONMEM) was used to assess the population pharmacokinetic model of amikacin in these patients. Apart from bodyweight and renal function, acute myeloblastic leukaemia and hypoalbuminaemia proved to be the most important covariates explaining the interindividual variability in amikacin pharmacokinetics in patients with haematological malignancies. The predictive performance of this population model for amikacin serum concentrations seems suitable for clinical purposes.
ISSN:0305-7453
1460-2091
DOI:10.1093/jac/44.2.235