Pharmacokinetic profile of imipenem/cilastatin in normal volunteers.

Imipenem is a new carbapenem antibiotic. It is coadministered with an equal amount of cilastatin, a dehydropeptidase-I inhibitor. Both drugs achieve similar serum concentrations in normal volunteers. Half-lives for both drugs are on the order of one hour and are excreted in the main into the urine. Cilastatin has been documented to have a metabolite, N-acetyl cilastatin, which can be recovered in the urine in an amount equivalent to approximately 12 percent of the administered dose of the parent compound. Less than 1 percent of a radiolabeled dose of either compound can be recovered in the feces, making clinically significant alterations of the fecal flora unlikely with the imipenem/cilastatin combination. Although probenecid causes only a minor effect on imipenem pharmacology, it increases the area under the curve and half-life of imipenem and decreases the renal clearance of cilastatin significantly. In view of the pharmacokinetic profile of imipenem/cilastatin, the microbiologic activity of imipenem, and the post-antibiotic effect of imipenem against Pseudomonas aeruginosa, imipenem/cilastatin has the potential to control the majority of bacteremic nosocomial pathogens.