Stability of vancomycin in large volume parenteral solution and/or in association with drugs: use of green fluorescent protein (GFP) as biosensor of stability

• Grant number: 06/01536-8
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2006
• End date: October 31, 2007
• Field of knowledge: Health Sciences - Pharmacy - Medicines Analysis and Control
• Principal Investigator: Leoberto Costa Tavares
• Grantee: Leoberto Costa Tavares
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The resistance of microorganisms to antimicrobial agents, which the best example is methicilin-resistant Staphylococcus aureus, MRSA strain, is considered a worldwide health public problem, due to the high levels of morbidity, mortality and easily spread wide.The vancomycin structure, first choice in the treatment of MRSA infections, is composed by seven amino acids, two sugar molecules and presents dissociation in six different pKas. The variation between the dissociate forms of this drug and its amino acids hydrophobicity in large volume parenteral solution (LVPS), which depends on the composition and pH values, interferes in the stability of the drug and in the treatment efficacy.Green Fluorescent Protein, GFP, expressed by E. coli DH5-alfa cells, is an excellent biological indicator due to its ability to be easily monitored in a wide variety of applications. Prior studies showed that GFP is sensible to the composition of LVPS, for example glucose and sodium chloride, their concentration and pH values.Characteristics of each system when joined in the same recipient can interfere in the drug stability and modify the expected therapeutic efficacy. This project aims evaluate the stability of vancomycin in LVPS and the stability of the system vancomycin- parenteral solution – GFP – patient, by variation of the fluorescence intensity of GFP, optimizing its use of vancomycin and the minimizing the incidence of resistant strains. (AU)