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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Disposition of radiolabeled imipenem and cilastatin in normal human volunteers.

In the first of two successive studies, four healthy male subjects received 500 mg of 14C-labeled imipenem alone and together with 500 mg of unlabeled cilastatin sodium. In the second study, the same subjects were given 250 mg of 14C-labeled cilastatin sodium alone and together with 250 and 1,000 mg of cold imipenem. Concentrations of imipenem and cilastatin in plasma, urine, and feces were assayed by high-pressure liquid chromatography and radiometry. Plasma concentrations of imipenem assayed radiometrically were higher than those measured by high-pressure liquid chromatography. In one subject studied at the end of drug administration, the open lactam metabolite of imipenem represented 9% of the radioactivity. Plasma levels of cilastatin determined by high-pressure liquid chromatography and radiometry were virtually identical. Urinary recovery of imipenem varied between 12 and 42% of the dose when that drug was given alone but increased to between 64 and 75% when administered with cilastatin sodium at a 1:1 ratio. Almost all radioactivity of imipenem was recovered in the urine within 96 h after drug administration. The open lactam metabolite, resulting from the metabolism of imipenem in the kidneys by a dipeptidase, dehydropeptidase-I, represented 80 to 90% of the effluent radioactivity when imipenem was given alone and about 20% when cilastatin sodium was coadministered. Renal excretion of cilastatin followed closely that of imipenem. Almost all of the administered radioactivity was recovered in 24 h, and about 75% of the dose was recovered as unchanged cilastatin within 6 h. The N-acetyl metabolite of cilastatin was found to represent about 12% of the total radioactivity.[1]


  1. Disposition of radiolabeled imipenem and cilastatin in normal human volunteers. Norrby, S.R., Rogers, J.D., Ferber, F., Jones, K.H., Zacchei, A.G., Weidner, L.L., Demetriades, J.L., Gravallese, D.A., Hsieh, J.Y. Antimicrob. Agents Chemother. (1984) [Pubmed]
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