Synthesis and properties of dextran-linked ampicillin.

Ampicillin was coupled to dextran of average molecular weight 9,000 or 81,200 via the cyanogen bromide method. The degree of drug substituted per glucose unit (DSG) was varied from 0.104 to 0.028 (by weight bases: 22.1-5.9%) depending on the ratio of the reactants. Water solubility of dextran-linked ampicillin increased compared with free ampicillin, and the solubility decreased as the amount of ampicillin substituted increased. Plasma concentration of ampicillin, which appeared after intravenous administration of dextran-linked ampicillin in rats, was higher than when free ampicillin was administered, and the more so, the higher the molecular weight of dextran. Plasma half-life of dextran-linked ampicillin was two times longer than that of free ampicillin in rats. Antibacterial activities of dextran-linked ampicillin were evaluated against Staphylococcus aureus, Bacillus substillis, and Escherichia coli at two concentration levels according to the cup-plate method by measuring the diameter of inhibition zone, which was comparable to that of free ampicillin.