Application of pharmacokinetic-pharmacodynamic model to optimize dosing regime of antimicrobial drug Grammidin containing gramicidin S
S. Smirnov(1), A. Belashov(2), O. Demin(3)
(1)Institute for Systems Biology SPb, Moscow, Russia, (2)Pharmaceutical company JSC “Valenta Pharmaceutics”, Moscow, Russia, (3)AN Belozersky Institute of Physico-chemical Biology, Moscow State University
Objectives: To predict the dependence of antimicrobial effect of the gramicidin S 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.
Methods: Mechanism based PK/PD modeling of antimicrobial effect of gramicidin S.
Results: The model has been employed to optimize dosing regime of the commercially available 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.
Conclusion: Based on the simulation results it has been found [1] that (1) two fold prolongation of prescribed resorption time (from 30 min to 60 min) of the Grammidin tablet comprising standard dosage of 3 mg of gramicidin S results in 1.5-fold increase in efficacy, (2) 1.5-fold decrease in gramicidin S dosage (from 3 mg to 2 mg per administration) under condition of holding prescribed resorption time (30 min) does not lead to any considerable decrease in the efficacy of the drug.
References:
[1] Smirnov S., Belashov A., Demin O. Optimization of antimicrobial drug gramicidin S dosing regime using biosimulations (2009) Europ J Pharmac Sciences. 36(1), 105-109.