Jongtae Lee1, Taegon Hong1, Sangil Jeon1, Seunghoon Han2, Dong-Seok Yim2, Heungjeong Woo3
1Department of Clinical Pharmacology and Therapeutics, Seoul St. Mary’s Hospital; 2Department of Pharmacology, College of Medicine, the Catholic University of Korea, Seoul, Korea; 3Department of Internal Medicine, Hangang Sacred Heart Hospital, Hallym University Medical Center, Seoul, Korea.
Objectives: Colistin is increasingly used as salvage therapy of nosocomial infections caused by multidrug-resistant gram-negative bacteria such as Psuedomonas aeruginosa and Acinetobacter baumannii. However, the available pharmacokinetic (PK) data of colistin are limited to guide dosing. The aim of this study was to develop a population PK model for colistin in burn patients.
Methods: Fifty patients with burns ranging from 4% to 85% of total body surface area treated with Colistimethate sodium (CMS) were studied. CMS which is hydrolyzed in vivo to the active metabolite was intravenously administered at a dose of 150mg every 12 h. Blood samples were collected right before and at 1, 2, 4, 6 and 8 h after more than five infusions. The population PK model was developed using a mixed effect method (NONMEM, ver. 6.2).
Results: A one-compartment linear PK model for colistin best described the data. Covariates included in the final model were creatinine clearance on the fraction of CMS converted into colistin and body weight on the central volume of colistin. The mean population pharmacokinetic parameters were clearance (5.79 L/h), volume of distribution (53.7 L), the turnover rate of CMS converted into colistin (0.766 – EDEMA x 0.429), the fraction of CMS converted into colistin (1 – 0.203 x EXP(CLcr /120)) with interindividual variability (CV%) of 35.4%, 25.5%, 68.6% and 0, respectively.
Conclusions: The PK of colistin have been characterized for the first time in burn patients after i.v. administration of CMS. The model-fitted parameter estimates may be applied to determine the optimal dosage regimens of colistin in burn patients.
Reference: PAGE 21 (2012) Abstr 2486 [www.page-meeting.org/?abstract=2486]
Poster: Infection