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The pharmacokinetics of polymyxin B 1 , polymyxin B 2 , colistin A, and colistin B were investigated in a rat model following intravenous administration (0.8 mg/kg) of each individual component. Plasma and urine concentrations were determined by LC-MS/MS, and plasma protein binding was measured by ultracentrifugation. Total and unbound pharmacokinetic parameters for each component were calculated using noncompartmental analysis. All of the polymyxin components had a similar clearance, volume of distribution, elimination half-life, and urinary recovery. The area under the concentration-time curve for polymyxins B 1 and B 2 was greater than those of colistins A and B. Colistin A (56.6 ± 9.25%) and colistin B (41.7 ± 12.4%) displayed lower plasma protein binding in rat plasma compared to polymyxin B 1 (82.3 ± 4.30%) and polymyxin B 2 (68.4 ± 3.50%). These differences in plasma protein binding potentially equate to significant differences in unbound pharmacokinetics, highlighting the need for more stringent standardization of the composition of commercial products currently available for clinical use.

Paenibacillus polymyxa JSa-9 had been found to produce five cyclic LI-F type antibiotics which were released into culture medium in accordance with our previous report. In this study, another three kinds of antagonistic compounds were extracted from P. polymyxa JSa-9 cell pellets and (or) spores by methanol. Using high performance liquid chromatography (HPLC) method, two antagonistic fractions were separated and collected from the methanol extract. One showed inhibition against Escherichia coli and Staphylococcus aureus, while the other was active against Aspergillus niger and S. aureus. By means of electrospray ionization mass spectroscopy (ESI-MS), infrared spectroscopy (IR), and amino acid analysis, two kinds of compounds from fraction B with molecular masses of 901 and 915Da were characterized as the linear lipopeptide analogs of antibiotics LI-F04a and LI-F04b, respectively. Another antimicrobial substance from fraction A could be attributed to polymyxin B(6)., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Two polymyxin antibiotics, polymyxins B and E (colistin), have been separated analytically into ten to thirteen components on a commercial reversed-phase material by isocratic elution with a mixture of acetonitrile, phosphate/formate and acetate buffer containing sodium sulphate and triethylamine. The analytical system was transferred to a preparative system, using a C18-bonded stationary phase, without extensive impairing of the selectivity. The major components of each product were isolated and characterized by high-performance liquid chromatography, amino acid analysis and identification of the fatty acid. Three components were isolated and characterized for the first time. The fatty acid was also identified in some of the minor components.