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.
D000328:Adult; D000900:Anti-Bacterial Agents / Q000097:blood* / Q000652:urine; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D015377:Cilastatin; D003521:Cyclopropanes / Q000097:blood* / Q000652:urine; D004361:Drug Tolerance; D005243:Feces / Q000032:analysis; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D015378:Imipenem; D007700:Kinetics; D008297:Male; D013845:Thienamycins / Q000097:blood* / Q000652:urine
D000900:Anti-Bacterial Agents; D003521:Cyclopropanes; D013845:Thienamycins; D015377:Cilastatin; D015378:Imipenem