[ English | Bahasa Malaysia ] Hari ini ialah 3 Aug 2020, 10:53 PM (Terakhir dikemaskini pada: 27th Jul 2020)

Text Red Text Black Text Blue Text Green Text Smaller Text Reset Text Larger

Publication Details
Year :


Journal :

Ami F. Mohamed, Otto Cars and Lena E. Friberg (2014). A pharmacokinetic/pharmacodynamic model developed for the effect of colistin on Pseudomonas aeruginosa in vitro with evaluation of population pharmacokinetic variability on simulated bacterial killing. Journal of Antimicrobial Chemotherapy 69(5): 1350-1361

Abstract :

Objectives: An optimized dosing regimen of the prodrug of colistin, colistin methanesulphonate (CMS), against resistant Pseudomonas aeruginosa is needed to ensure effective bacterial killing. The objectives of this study were to develop a pharmacokinetic (PK)/pharmacodynamic (PD) model that characterizes the time course of the antibacterial activity of colistin against P. aeruginosa in a static in vitro system and to perform simulations of different dosing regimens and dosing algorithms to evaluate the effect of interindividual variability and interoccasion variability in PK on bacterial killing.

Methods: Static in vitro time-kill curve experiments were conducted on two different strains of P. aeruginosa (MIC 1 and 1.5 mg/L). Mechanism-based PK/PD models were fitted in NONMEM7 and the final model was combined with a previously developed population PK model of CMS and colistin to perform simulations of variability based on different dosing algorithms.

Results: A model with compartments for growing and resting bacteria, with a function allowing the maximal bacterial killing of colistin to reduce upon increasing colistin exposure, characterized both the fast bactericidal effect and the adaptive resistance. The variability in PK was shown to translate into pronounced interoccasion variability in bacterial killing. A flat fixed loading dose was demonstrated to result in less variability than an algorithm based on weight.

Conclusions: The developed PK/PD model described the growth, death and resistance development of P. aeruginosa in response to colistin for two different strains. Based on simulations, a flat fixed loading dose followed by an 8 or 12 hourly maintenance dose with an infusion duration of up to 2 h appeared adequate.




IMR ialah sebuah organisasi bertauliah oleh SIRIM (nombor sijil 2972).

Laman ini sesuai dilihat menggunakan Firefox (24.0) dengan resolusi 1280 x 768 pixels atau lebih.

Lokasi Kami


Kami terletak di Jalan Pahang, 50588 Kuala Lumpur, Malaysia. Kami beroperasi dari jam 8.00pg - 5.00ptg Isnin - Jumaat. Klik pada imej peta untuk melancarkan servis Google Maps.

Hubungi Kami