Mutual pro-drugs of the olivanic acids and renal dipeptidase inhibitors.

The carbapenem antibiotics, which include the olivanic acids and thienamycin, possess potent broad spectrum antibacterial activity. They are however extensively metabolized by the renal dipeptidase enzyme, dehydropeptidase I. As a result of this degradation, only low urinary recoveries of antibiotic are obtained in vivo. The preparation of mutual pro-drugs of the olivanic acids and an inhibitor of the renal dipeptidase enzyme is described. MM 22382 and MM 13902 have been combined with Z-2-isovaleramidobut-2-enoic acid as double esters of formaldehyde hydrate. Administration of these linked esters to mice results in improved urinary recoveries of antibiotic.