Optimization of antimicrobial drug gramicidin S dosing regime using biosimulations.
In this paper we have developed a model of antimicrobial effect of gramicidin S. This model has allowed us to predict the dependence of antimicrobial effect of the drug applied as oral melting tablets on dosage, time of resorption and minimal inhibitory concentration (MIC) of the drug characterizing its ability to kill different bacteria. The model has been employed to optimize dosing regime of gramicidin S containing drug Grammidin. Efficacy of the drug has been studied for the diverse gram-positive and gram-negative bacteria with different MIC. The number of bacteria located in the oral cavity and killed by one-pass administration of the drug (resolution of one tablet) has been calculated under condition of various dosing regimes. Based on the simulation results it has been found that (1) twofold prolongation of prescribed resorption time (from 30 to 60min) of the tablet comprising standard dosage of 3mg of gramicidin S results in 1.5-fold increase in efficacy, (2) 1.5-fold decrease in gramicidin S dosage (from 3 to 2mg per administration) under condition of holding prescribed resorption time (30min) does not lead to any considerable decrease in the efficacy of the drug.
Smirnov
S
S
Institute for Systems Biology SPb, Moscow, Russia.
Belashov
A
A
Demin
O
O
D000465:Algorithms; D000891:Anti-Infective Agents, Local / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D003198:Computer Simulation; D006096:Gramicidin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D008826:Microbial Sensitivity Tests; D015233:Models, Statistical; D009055:Mouth / Q000382:microbiology; D013607:Tablets
D000891:Anti-Infective Agents, Local; D013607:Tablets; D006096:Gramicidin