ABSTRACT
The high interindividual variability in the pharmacokinetics (PK) of linezolid has been described, which results in an unacceptably high proportion of patients with either suboptimal or potentially toxic concentrations following the administration of a fixed regimen. The aim of this study was to develop a population pharmacokinetic model of linezolid and use this to build and validate alogorithms for individualized dosing. A retrospective pharmacokinetic analysis was performed using data from 338 hospitalized patients (65.4% male, 65.5 [±14.6] years) who underwent routine therapeutic drug monitoring for linezolid. Linezolid concentrations were analyzed by using high-performance liquid chromatography. Population pharmacokinetic modeling was performed using a nonparametric methodology with Pmetrics, and Monte Carlo simulations were employed to calculate the 100% time >MIC after the administration of a fixed regimen of 600 mg administered every 12 h (q12h) intravenously (i.v.). The dose of linezolid needed to achieve a PTA ≥ 90% for all susceptible isolates classified according to EUCAST was estimated to be as high as 2,400 mg q12h, which is 4 times higher than the maximum licensed linezolid dose. The final PK model was then used to construct software for dosage individualization, and the performance of the software was assessed using 10 new patients not used to construct the original population PK model. A three-compartment model with an absorptive compartment with zero-order i.v. input and first-order clearance from the central compartment best described the data. The dose optimization software tracked patients with a high degree of accuracy. The software may be a clinically useful tool to adjust linezolid dosages in real time to achieve prespecified drug exposure targets. A further prospective study is needed to examine the potential clinical utility of individualized therapy.
Subject(s)
Anti-Bacterial Agents , Anti-Bacterial Agents/therapeutic use , Female , Humans , Linezolid , Male , Monte Carlo Method , Prospective Studies , Retrospective StudiesABSTRACT
No disponible
Subject(s)
Humans , Quality of Life , Critical Care/trends , Critical Care/trends , Acute Disease/epidemiologyABSTRACT
We have analyzed the 57 ARDS admitted at the Intensive Care Unit (ICU) of the Hospital General Vall d'Hebron of Barcelona in 1996 (the 5.7% of the ICU and the 0.18% of the hospital admission). We have studied the epidemiological characteristics, as well as their ICU complications and mortality. This year was the first to have nitric oxide (NO) as complementary treatment in the ARDS patients at our hospital. They were 42 males and 15 females, with a mean age of 60 years, APACHE II 21 and a lung injury score 3.1. The 87% of the patients need vasoactive drugs. The 47% need Swan-Ganz catheter to optimize the haemodynamic management. The 77% presented a multiple organ disfunction syndrome (MODS) and the 56% acute renal failure. The total mortality was 70%, basically due to MODS (68%), while due to hypoxemia only in the 22%. The group treated with NO (the 35% of the ARDS patients) were younger, without any other differences the patients who did not received this treatment and with the same stage and mortality. Patients who presented MODS, renal failure or hemodynamic unstableness presented a higher mortality (p < 0.05).
