Imipenem discovery

Birnbaum J, Kahan FM, Kropp H, MacDonald JS. Carbapenems, a new class of beta-lactam antibiotics. Discovery and development of imipenem/cilastatin. Am J Med 1985 78(6A) 3-21. 

In 1985, the self-inactivating property of thienamycin was overcome by the use of a terminal imino functionality which is less nudeophilic. Imipenem (Fig. 22.32) has a broad spectrum of activity and is administered by deep intramuscular injection or as an intravenous infusion. Renal dehydropeptidase 1, an enzyme present in the kidney, attacks and inactivates imipenem. This problem has been overcome by the co-administration of imipenem with cilastatin, a renal dehydropeptidase 1 inhibitor. Mer-openem (Fig. 22.32), an analogue introduced in 1996, is stable to the action of renal dehydropeptidase 1 and is also administered by deep intramuscular injection or as an intravenous infusion. Since the discovery of thienamycin in 1976, only parenteral analogues have heen successfully used clinically because the carhapenem structure is unstable in both the stomach and intestine. 

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