Mutual pro-drugs of beta-lactam antibiotics and beta-lactamase inhibitors.
The principle of combining a beta-lactam antibiotic with a beta-lactamase inhibitor in a single molecule functioning as pro-drug for the two active components is illustrated by the linked esters 3 and 4 in which ampicillin and mecillinam, respectively, are combined with the beta-lactamase inhibitor penicillanic acid sulfone. It is shown that in man these esters are excellently absorbed from the gastro-intestinal tract and after absorption hydrolyzed with simultaneous liberation of the active components. As a result high blood and tissue levels of antibiotic and beta-lactamase inhibitor in a balanced ratio are attained. The advantages of "mutual pro-drugs" over simple combinations are discussed.
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D006801:Humans; D006868:Hydrolysis; D007408:Intestinal Absorption; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams