SAIVIN S, RIZO M, LAVIT M, GEORGES B, CONIL J, HOUIN G; Interscience Conference on Antimicrobial Agents and Chemotherapy (42nd : 2002 : San Diego, Calif.).
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2002 Sep 27-30; 42: abstract no. A-1416.
Lab Pharmacocinetique, Toulouse, France.
BACKGROUND: Amikacin (AMIK) is one of the most useful aminoglycoside in the treatment of G-negative infections. Intensive care unit's (ICU) patients present a large pharmacokinetic (PK) variability. The aim of our study was to provide for therapeutic drug monitoring a population PK model by using sparse data collected during routine clinical care. Material and methods: AMIK was administered intravenously over 0.5 h, once daily. A mixed-effect modelling approach was used to fit the data from 59 patients (201 concentrations). Demographics, clinical and biological covariates were tested for evaluating their influence on PK parameters. A second group of 23 patients (92 concentrations) was used for the validation, its covariates did not statistically differ from those of the first population. RESULTS: An open two-compartment PK model was used. The statistical model chosen to describe the inter-individual variability (IIV) and the residual error was proportional. The model including weight (WT), creatinine clearance (CLCR), PLA2, simplified acute physiology score I (IGS1) was used to predict AMIK concentrations in the validation group. To determine its predictive performance we compared the mean +/- SD observed (18,2 +/- 19,9 mg/L) and predicted values (18,8 +/- 20,0 mg/L) by computing bias (0,618; IC: -1,338; 2,574), precision (9,54 mg/L), average fold error (1,63) and correlation (r=0,8850). The mean population parameters and their IIV (CV %) obtained for the 82 patients are as follows: clearance (3 L/h, 28%), initial volume of distribution (22 L, 18%), inter-compartmental clearance (4.3 L/h, 73%) and peripheral volume of distribution (66 L, 59%). Discussion: The validation was achieved. The mean values obtained for AMIK PK parameters are consistent with reported values in ICU patients. The covariates included in the model explain a part of the IIV in the PK parameters. Our model permits to adjust AMIK dosage regimen in clinical routine.
Publication Types:
Keywords:
- Amikacin
- Anti-Bacterial Agents
- Body Size
- Demography
- Humans
- Intensive Care Units
- Models, Biological
- Models, Statistical
- Population
- Population Groups
- pharmacokinetics
Other ID:
UI: 102266614
From Meeting Abstracts