Optimised dosing of vancomycin in critically ill Indigenous Australian patients with severe sepsis

This study aimed to describe the pharmacokinetics (PK) of vancomycin in Australian Indigenous patients with severe sepsis, and advise an optimal dosing strategy. A population PK study was conducted in a remote Australian intensive care unit (ICU). Serial plasma samples were collected over one to two dosing intervals and assayed by validated chromatography. Concentration –time data collected were analysed using Pmetrics® software. The final population PK model was then used for Monte Carlo dosing simulations to determine optimal loading and intermittent maintenance doses. Fifteen Indigenous subjects were included for analysis with a median (interquartile range, I QR) age, weight and creatinine clearance (CrCL) of 43 (34–46) years, 73 (66–104) kg and 99 (56–139) ml/minute respectively. A two-compartment model described the data adequately. Vancomycin clearance (CL) and volume of distribution of the central compartment (Vc) were described by CrCL and pat ient weight respectively. Median (IQR) CL, Vc, distribution rate constants from central to peripheral, and from peripheral to central compartments were 4.6 (3.8–5.6) litres per hour, 25.4 (16.1–31.3) litres, 0.46 (0.28–0.52)/hour and 0.25 (0.12–0.37)/hour respectively. No significant interet hnic PK differences were observed in comparison to published data. Therapeutic loading doses were significantly dependent on both weight and CrCL, whereas maintenance doses were dependent on CrCL. In the absence of severe re...
Source: Anaesthesia and Intensive Care - Category: Anesthesiology Source Type: research